Search Results

PSEN2 (90)

Mutation	Pathogenicity	DNA Change	Expected RNA \| Protein Consequence	Coding/Non-Coding	Genomic Region	Neuropathology	Biological Effect	Primary Papers
T18M	AD : Benign, PD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 4	Unknown.	Unknown; predicted pathogenic in silico (CADD>20).	Blauwendraat et al., 2016
A23A	AD : Benign	Substitution	Substitution \| Silent	Coding	Exon 4	Unknown.	Unknown, but in silico algorithm predicted non-deleterious (CADD = 5.75).	Eryilmaz et al., 2021
R29H	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 4	Not applicable.	Unknown.	Guerreiro et al., 2010
G34S	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 4	Unknown, but in one case, brain MRI showed multiple ischemic foci of the bilateral frontal-parietal lobe and brain atrophy.	Unchanged Aβ42/Aβ40 ratio.	Sleegers et al., 2004
N43N	AD : Benign	Substitution	Substitution \| Silent	Coding	Exon 4	Unknown.	Unknown.	Eryilmaz et al., 2021
R62C	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown.	Reduced levels of CSF Aβ43 and Aβ42, and increased Aβ40; decreased Aβ42/Aβ40 ratio in one carrier.	Sleegers et al., 2004
R62H	AD : Benign, FTD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown. In two carriers, CSF biomarker levels were variable.	In two carriers, CSF Aβ peptide levels were variable. In cells, unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	Cruts et al., 1998; Gallo et al., 2010
C65Y	svPPA : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown. In one case, CSF biomarkers (Aβ42, tau, and phospho-tau) were inconsistent with AD.	Unknown. In silico predictions were mixed (PHRED-scaled CADD = 19.4).	Ramos-Campoy et al., 2020
P69A	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown.	Unknown, but scored low for deleteriousness in silico (PHRED-scaled CADD <20).	Dobricic et al., 2012
R71W	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 5	Leukoencephalopathy with periventricular white-matter lacunar infarctions.	Unchanged Aβ42/Aβ40 ratio; Reduces the stability of the presenilin-2 protein and impairs Notch signaling.	Sleegers et al., 2004
L79P	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown, but CSF biomarkers consistent with AD.	Unknown, but some in silico algorithms predicted damaging (PHRED-scaled CADD>20).	Ramos-Campoy et al., 2020
K82R	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown; neuroimaging showed diffuse cortical atrophy, especially in the posterior region and mild hippocampal atrophy. FDG-PET showed widespread hypometabolism. PIB-PET showed amyloid deposition in the frontal lobe, lateral temporal lobe, parietal lobe, posterior cingulate cortex, precuneus, and striatum.	Aβ42/Aβ40 ratio, and Aβ42 and Aβ40 secretion similar to control in cellular assay.	Shi et al., 2015
K82fs	Tauopathy consistent with Pick's Disease : Not Classified	Deletion	Deletion \| Frame Shift	Coding	Exon 5	Neuropathology consistent with Pick's disease.	Frameshift starting at K82; reduced mutant protein in frontal cortex and hippocampus.	Perrone et al., 2018
A85V	AD : Uncertain Significance, DLB : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 5	In one carrier: amyloid deposition; neurofibrillary changes; diffuse Lewy bodies in the neocortex.	Decreased Aβ37/Aβ42 ratio, and moderately increased or unchanged Aβ42/Aβ40 ratio, in transfected cells. Fragmentation and altered function of mitochondria in iPSC neurons.	Piscopo et al., 2008
I100I	AD : Likely Benign	Substitution	Substitution \| Silent	Coding	Exon 5	Unknown.	Unknown, but predicted benign in silico (PHRED-scaled CADD score = 6.52).	Wang et al., 2023
V101M	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 5	Unknown.	Unknown; predicted probably damaging in silico.	Sala Frigerio et al., 2015
K115Efs* (K115Efx10)	AD : Uncertain Significance	Deletion	Splicing Alteration \| Frame Shift	Coding	Exon 5	Neuropathology was consistent with AD.	The deletion of two nucleotides from exon 5 leads to a frameshift and ultimately to a premature stop codon in exon 6. In patient fibroblasts, secretion of Aβ40 was decreased, and Aβ38 and Aβ42 were undetectable. Wild-type PSEN2 levels were also decreased. Alternatively spliced transcripts of the mutant allele were detected in brain.	Jayadev et al., 2010
G117Ter (G117X)	AD : Not Classified	Substitution	Substitution \| Nonsense	Coding	Exon 5	Unknown	Unknown, but in silico prediction of deleteriousness was high (CADD = 40).	Mao et al., 2021
T122P	AD : Likely Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	Finckh et al., 2000
T122R	Atypical Dementia : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Variable cortical and subcortical atrophy.	Increased Aβ42/Aβ40 ratio and decreased Aβ37/Aβ42 ratio in cells. Reduced calcium ion released from intracellular stores.	Binetti et al., 2003
P123L	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown; Neuroimaging showed diffuse cortical atrophy, predominantly in the right hemisphere. FDG-PET showed hypoperfusion in the right temporal and parietal regions.	Increased Aβ42 and decreased Aβ40 secretion in cells, resulting in an approximately 2-fold increase in the Aβ42/Aβ40 ratio. Decreased Aβ37/Aβ42 ratio.	Xia et al., 2015
E126K	AD : Likely Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown.	Increased Aβ42/Aβ40 ratio and decreased Aβ37/Aβ42 ratio in cells.	Müller et al., 2014
E126fs	AD : Not Classified	Insertion	Insertion \| Frame Shift	Coding	Exon 6	Unknown; neuroimaging showed hippocampal and parahippocampal atrophy.	Reduced Aβ42 and Aβ40 secretion, as well as the Aβ42/Aβ40 ratio in a cellular assay.	El Kadmiri et al., 2014
S130L	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 6	Neuropathology consistent with AD at autopsy in at least one case. Reduced CSF Aβ43/Aβ40 and Aβ42/Aβ40 ratios in another case, with slightly elevated tau and normal phospho-tau CSF levels.	In transfected cells, unchanged Aβ42/Aβ40 ratio, Aβ42, PSEN2-CTF, and PSEN2-NTF. Altered calcium signaling in cells.	Sorbi et al., 2002; Tedde et al., 2003
L135R	FTD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but PHRED-scaled CADD score was above 20 suggesting a damaging effect.	Koriath et al., 2018
V139M	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 6	Bilateral hypoperfusion in the parietal-temporal lobes.	In transfected cells, Aβ42 and Aβ40 levels, as well as Aβ42/Aβ40 ratio, were not significantly different from control.	Bernardi et al., 2008
N141Y	AD : Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 6	Proband had autopsy-confirmed AD with severe brain atrophy and numerous plaques and neurofibrillary tangles.	Increased Aβ42/Aβ40 ratio and decreased Aβ37/Aβ42 ratio in cultured cells.	Niu et al., 2014
N141D	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but 3 algorithms predict damaging with a PHRED CADD score of 24.9.	Wang et al., 2019
N141I	AD : Pathogenic	Substitution	Splicing Alteration; Substitution \| Deletion; Missense	Coding	Exon 6	Extensive amyloid plaques; Extensive neurofibrillary tangles (typically a Braak score of V or VI); α-synuclein inclusions, especially in the amygdala; Rare TDP-43 pathology; Hippocampal sclerosis.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in PSEN2-CTF and PSEN2-NTF. Altered microglial phenotype. In 3-D brain organoids, elevated Aβ42/Aβ40 ratio, asynchronous calcium transients, and neuronal hyperactivity. Cytokine overproduction in mice. Exon 6 skipping in ~10% of mutated transcripts, reduced mRNA stability.	Levy-Lahad et al., 1995; Rogaev et al., 1995; Morales et al., 2024
N141S	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown.	Unknown, but in silico algorithms predicted damaging (CADD > 20).	Mao et al., 2021
L143H	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Not applicable.	Unknown, but in silico analysis predicts a deleterious effect (PHRED-scaled CADD > 20).	Guerreiro et al., 2010
I146T	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but predicted damaging in silico (CADD > 20).	Mao et al., 2021
S147N	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but in silico analyses predicted damaging (CADD>20).	Mao et al., 2021
V148I	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown.	Mixed results in cells. Aβ42/Aβ40 ratio increased or unchanged; Aβ37/Aβ42 decreased. No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	Lao et al., 1998
I149T	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but in silico analysis predicts a damaging effect (PHRED-scaled CADD >20).	Perrone et al., 2020
V150M	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but predicted damaging in silico (PHRED-scaled CADD score >20).	Gao et al., 2019
T153S	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but in silico analysis suggests damaging effect (PHRED-scaled CADD score =25.9).	Perrone et al., 2020
K161R	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown.	Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD score = 32).	Wallon et al., 2012
R163C	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 6	Unknown	Unknown, but predicted damaging by in silico algorithms.	Gao et al., 2019
R163H	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 6	Not applicable.	Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD score > 20).	Puschmann et al., 2009
H169N	AD : Uncertain Significance, FTD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 7	Unknown; neuroimaging showed mild atrophy and widespread hypometabolism. PIB-PET showed amyloid deposition in the AD case, but no amyloid deposition in the FTD case.	Unknown.	Shi et al., 2015
M174V	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 7	Unknown; imaging has shown frontal atrophy and hypoperfusion in temporoparietal regions.	Decreased Aβ40 modestly without significantly changing the Aβ42/Aβ40 ratio in a cell assay.	Andreoli et al., 2008; Clarimón et al., 2008; Guerreiro et al., 2010
M174I	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 7	Neuropathology consistent with AD.	Unknown, but in silico algorithm predicted damaging (PHRED-scaled CADD > 20).	Wong et al., 2020
S175C	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 7	Unknown; MRI showed focal atrophy in the medial temporal lobe; SPECT showed bilateral hypoperfusion in temporoparietal regions.	Unknown, but in silico analyses predicted a damaging effect (PHRED-scaled CADD score > 20).	Piscopo et al., 2010
S175F	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 7	Unknown, but in one case brain imaging showed atrophy and hypometabolism consistent with AD.	Unknown, but multiple in silico algorithms suggest it is damaging.	Guven et al., 2021
F183S	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 7	Unknown.	Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD score >20).	Wojtas et al., 2012
Y195C	FTD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown	Unknown, but the PHRED-scaled CADD score was > 20 suggesting a damaging effect.	Koriath et al., 2018
G212V	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Neuropathology consistent with AD.	Unknown; predicted pathogenic in silico (PHRED-scaled CADD score = 27.7).	Marín-Muñoz et al., 2016
V214L	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown; neuroimaging showed diffuse cortical atrophy and widespread hypometabolism.	Unknown; structural changes were predicted in silico, especially at amino acids 214, 219, and 220. PolyPhen2 predicted a probably or possibly damaging effect; PHRED-scaled CADD score = 24.3.	Youn et al., 2014
H220Y	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown	Unknown, but in silico algorithms predict damaging (CADD > 20).	Mao et al., 2021
L225P	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown.	Unknown, but PHRED-scaled CADD score was above 20, suggesting a damaging effect.	Koriath et al., 2018
Q228L	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown.	Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD score >20).	Zekanowski et al., 2003
Y231C	FTD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown; MRI showed diffuse subcortical and cortical atrophy, particularly in the frontotemporoparietal lobes.	Unknown but in silico analysis predicted a damaging effect (PHRED-scaled CADD score = 27.8).	Marcon et al., 2009
I235F	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown.	Increased Aβ42/Aβ40 ratio in cells.	Lee et al., 2014
S236S	AD : Benign	Substitution	Splicing Alteration \| Silent	Coding	Exon 8	Unknown, but in one patient PET showed amyloid deposition and MRI revealed atrophy in temporo-insular cortices. FDG-PET showed diffuse hypometabolism in the cortex and striatum.	Unknown. In silico analyis predicted it is benign (PHRED-scaled CADD = 7.2), but could alter splicing.	Coppola et al., 2020
A237V	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 8	Neuropathology consistent with AD.	Unknown; predicted possibly damaging in silico.	Sassi et al., 2014
L238F	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown.	Increased Aβ42/Aβ40 ratio in cellular assay.	Sala Frigerio et al., 2015
L238P	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown; MRI showed supratentorial cortical atrophy, particularly atrophy of the parietal cortex.	Unknown; predicted damaging in silico (PHRED-scaled CADD score = 26.7).	Blauwendraat et al., 2016
M239V	AD : Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 8	Diffuse cerebral atrophy; Senile plaques; Neurofibrillary tangles (stage VI of Braak and Braak); Ectopic neurons in the subcortical white matter; Extracellular "ghost" neurofibrillary tangles.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	Rogaev et al., 1995
M239T	AD : Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown, but florbetapir-PET indicated amyloid accumulation in one carrier and CSF biomarkers were consistent with AD in another. Atrophy of the parietal lobe was observed in both patients, with one of them also having occipital cortex atrophy. In the latter patient, FDG-PET suggested hypometabolism in parietal, temporal, and occipital cortices.	Increased Aβ42 and Aβ42/Aβ40 ratio in cells.	Li et al., 2021; Jiao et al., 2021; Mao et al., 2021
M239I	AD : Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 8	Moderate cortical atrophy; Numerous neurofibrillary tangles; Numerous senile plaques, especially in the amygdala.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF; Reduced calcium release.	Finckh et al., 2000
A252T	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 8	Not applicable.	Decreased Aβ42 and Aβ40 in cells, without altering Aβ42/Aβ40 ratio.	Guerreiro et al., 2010
A258T	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 8	Not applicable.	Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD = 26.8).	Sala Frigerio et al., 2015
A258V	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 8	Unknown	Reduced Aβ40 and Aβ42 in a cellular assay without affecting the Aβ42/Aβ40 ratio.	Yagi et al., 2014
R284G	AD : Likely Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 9	Unknown.	Increased Aβ42 and Aβ42/Aβ40 in a cell assay.	Lanoiselée et al., 2017
P287P	AD : Likely Benign	Substitution	Substitution \| Silent	Coding	Exon 9	Unknown, but associated with increased glucose metabolism in the bilateral fronto-temporo-parietal cortices.	Unknown, but in silico analysis did not predict a damaging effect (PHRED-scaled CADD = 11.4).	Jia et al., 2020
c.887-3C>T	AD : Not Classified	Substitution	Splicing Alteration \|	Non-Coding	Intron 9	Unknown	Unknown, but in silico analysis does not predict a damaging effect (PHRED-scaled CADD score of 9.977).	Wang et al., 2019
M298T	AD : Likely Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 10	Unknown.	Unknown. Some, but not all, in silico algorithms predicted damaging (PHRED-scaled CADD>20).	Wang et al., 2019
T301M	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 10	Unknown.	Unchanged Aβ42/Aβ40 ratio.	Croes et al., 2004
K306fs	AD : Not Classified	Deletion	Deletion \| Frame Shift	Coding	Exon 10	Unknown; neuroimaging in one case showed cortical atrophy.	Unknown; the deletion of a single nucleotide (A) in exon 9 is predicted to result in a frameshift at codon 306.	El Kadmiri et al., 2014
P334A	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 11	Not applicable.	Moderately decreased Aβ40 without changing Aβ42/Aβ40 ratio.	Lee et al., 2014
P334R	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 11	Not applicable.	Unknown, but predicted not damaging in silico (PHRED-scaled CADD score = 16.3).	Lleó et al., 2002
P348L	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 11	Unknown.	Decreased Aβ40; increased Aβ42/Aβ40 ratio in cell assay.	Blauwendraat et al., 2016
G359Lfs*74 (Intron 11 delA)	AD : Not Classified, MCI : Not Classified	Deletion	Splicing Alteration \| Deletion; Frame Shift	Both	Intron 11	Unknown, but MRI of MCI patient revealed mild atrophy in the hippocampus, and SPECT showed decreased metabolism in posterior and temporal cortices.	Deletion of an adenine in intron 11 resulting in exon 12 skipping and a frameshift starting at codon G359; new termination codon in the 3' UTR. Reduced PSEN2 levels due to instability. CADD-PHRED = 23.9.	Perrone et al., 2018
G359Lfs*74 (Intron 11 delAG)	ALS : Not Classified	Deletion	Splicing Alteration \| Deletion; Frame Shift	Both	Intron 11	Unknown.	Deletion of an adenine in intron 11 resulting in exon 12 skipping and a frameshift starting at codon G359; new termination codon in the 3' UTR.	Perrone et al., 2018
I368F	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 12	Unknown	Unknown, but multiple in silico algorithms predicted a damaging effect (PHRED-scaled CADD >20).	Mao et al., 2021
F369S	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 12	Unknown, but MRI in one case showed progressive brain atrophy, particularly in the temporal lobe and hippocampus.	Unknown, but in silico algorithms predict damaging effect (CADD > 20)	Wan et al., 2021
A377V	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 12	Not applicable.	Unknown.	Lee et al., 2014
A379D	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 12	Unknown	Unknown, but predicted damaging in silico. PHREDD CADD score = 27.1	Wang et al., 2019
T388M	bvFTD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 12	Unknown. CSF biomarker levels (Aβ42, tau, phospho-tau) were not consistent with AD.	Unknown, but multiple in silico algorithms predicted damaging (CADD >20).	Ramos-Campoy et al., 2020
C391R	MCI : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 12	Unknown.	Unknown, but PHRED-scaled CADD = 28.6, suggesting a deleterious effect.	Mathioudakis et al., 2023
V393M	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 12	Unknown; bilateral hypometabolism in the parieto-occipital regions.	Unchanged Aβ42/Aβ40 ratio in cells. In one assay, reduced secretion of Aβ4 and Aβ42, in another, Aβ42 secretion was unchanged.	Lindquist et al., 2008
A394Pfs*8	AD : Not Classified	Deletion	Deletion \| Frame Shift	Coding	Exon 12	Unknown	Unknown	Jiao et al., 2021
A415S	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 13	Unknown, but MRI revealed global cerebral and cerebellar atrophy. CSF biomarkers were consistent with AD.	Unknown, but in silico algorithm predicted damaging (PHRED-scaled CADD > 20).	Wong et al., 2020
T421M	AD : Benign	Substitution	Substitution \| Missense	Coding	Exon 13	Unknown	Decreased both Aβ42 and Aβ40, without affecting Aβ42/Aβ40 ratio in cellular assay.	Yagi et al., 2014
T430M	AD : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 13	Right frontotemporal hypoperfusion.	Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD score = 31).	Ezquerra et al., 2003
R435Q	AD : Uncertain Significance	Substitution	Substitution \| Missense	Coding	Exon 13	Unknown.	Unknown, but in silico algorithms predict damaging (PHRED-scaled CADD = 22.1).
P436L	Dementia : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 13	Unknown, but MRI of one carrier showed bilateral atrophy of the temporal lobe and hippocampus.	Unknown.	Han et al., 2020
D439A	AD : Likely Benign	Substitution	Substitution \| Missense	Coding	Exon 13	Unknown; imaging showed moderate cortical atrophy in the frontal and parietal regions.	MIxed results in vitro.	Lleó et al., 2001
c.*71C>A	AD : Likely Pathogenic	Substitution	Substitution \|	Non-Coding	Exon 13, 3'UTR	Unknown, but MRI scan of one case showed widening of the sulcus, fissure, and temporal horn, with decreased hippocampal volume. Also, FDG-PET showed hypometabolism in the bilateral frontal, parietal, and temporal lobes. Five affected carriers had CSF Aβ42, total tau, and phospho-tau consistent with AD.	Reduction of binding of PSEN2 expression suppressor miR-183-5p, possibly causing increased Aβ42/Aβ40 ratio.	Pang et al., 2021; Jia et al., 2020

Mutations

PSEN-2

Search Results

PSEN2 (90)