Mutations

PSEN2 R163C

Overview

Pathogenicity: Alzheimer's Disease : Uncertain Significance
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227073369 C>T
dbSNP ID: rs200931244
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CGC to TGC
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 6

Findings

This mutation was found in a screen of APP, PSEN1, and PSEN2 genes of 148 Chinese patients with familial Alzheimer’s disease (AD) (Gao et al., 2019). Two carriers from two different families were identified: a 74-year-old woman who was 69 at age of onset and an 80-year-old man who was 77 at onset. Both probands suffered from memory loss, disorientation, dyscalculia, and deficits in visuospatial skills. The man also had executive dysfunction and anxiety. The APOE genotype of the woman was APOE3/APOE3, while that of the man was APOE3/APOE4. The variant was reported absent from the gnomAD variant database, but was found at a frequency of 0.00000809 in a more recent database search (two alleles in European individuals, gnomAD v2.1.1, August 2020). 

Neuropathology
Unknown

Biological effect
The biological effect of this mutation is unknown, but in silico algorithms predicted the mutation to be probably damaging (PolyPhen), affecting protein function (SIFT), and disease-causing (MutationTaster), with a CADD score of 35. The authors classified the mutation as “probably pathogenic,” following the algorithm by Guerreiro et al., 2010.

Last Updated: 04 Nov 2021

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

  1. . Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease. Neurobiol Aging. 2019 May;77:154-157. Epub 2019 Jan 31 PubMed.
  2. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.

External Citations

  1. gnomAD v2.1.1, August 2020

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer's disease. Neurobiol Aging. 2019 May;77:154-157. Epub 2019 Jan 31 PubMed.

Other mutations at this position

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.