Mutations

PSEN2 H220Y

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227076621 C>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CAC to TAC
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 8

Findings

This variant was found in a Han Chinese woman with Alzheimer’s disease and no known family history of dementia (Mao et al., 2021). Her age at onset was 65 years. Her APOE genotype was APOE3/E3.

This mutation was absent from the gnomAD variant database (v2.1.1, Oct 2021).

Neuropathology
Unknown.

Biological Effect
In silico algorithms (SIFT, Polyphen, and LRT) predicted a damaging effect for this variant (Mao et al., 2021) and, consistently, its PHRED-scaled CADD score, which integrates diverse information in silico, was above the commonly used deleteriousness threshold of 20 (CADD v.1.6, Oct 2021). Mao and colleagues classified this as a variant of uncertain significance using the ACMG guidelines (Richards et al., 2015).

Last Updated: 26 Oct 2021

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References

Paper Citations

  1. . Clinical Phenotype and Mutation Spectrum of Alzheimer's Disease with Causative Genetic Mutation in a Chinese Cohort. Curr Alzheimer Res. 2021;18(3):265-272. PubMed.
  2. . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. Epub 2015 Mar 5 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Clinical Phenotype and Mutation Spectrum of Alzheimer's Disease with Causative Genetic Mutation in a Chinese Cohort. Curr Alzheimer Res. 2021;18(3):265-272. PubMed.

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