Mutations

PSEN2 A377V

Overview

Pathogenicity: Alzheimer's Disease : Benign
Clinical Phenotype: Alzheimer's Disease, None
Reference Assembly: GRCh37/hg19
Position: Chr1:227081765 C>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCG to GTG
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 12

Findings

This variant in PSEN2 was identified in one out of 184 probands representing Caribbean Hispanic families affected by familial Alzheimer’s disease (Lee et al., 2014). The mutation was also observed in two of nine unaffected family members, and therefore does not appear to segregate with disease. The proband met NINCDS-ADRDA criteria for probable AD, but further clinical details were not reported. Note, this variant was reported as PSEN2 A344V, but the nucleotide change observed corresponds to A377V in the reference isoform of presenilin-2.

Twelve heterozygotes were reported in the gnomAD variant database. Although most (eight) were of non-Finnish European ancestry, two were members of the Latino/Admixed American population (gnomAD v2.1.1, Nov 2021).

Neuropathology

Not applicable.

Biological Effect

The biological effects of this variant are unknown, but its PHRED-scaled CADD score, which integrates diverse information in silico, was above 20, suggesting a deleterious effect (CADD v.1.6, Nov 2021).

Last Updated: 10 Nov 2021

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References

Paper Citations

  1. . Disease-related mutations among Caribbean Hispanics with familial dementia. Mol Genet Genomic Med. 2014 Sep;2(5):430-7. Epub 2014 Jun 4 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Disease-related mutations among Caribbean Hispanics with familial dementia. Mol Genet Genomic Med. 2014 Sep;2(5):430-7. Epub 2014 Jun 4 PubMed.

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