Mutations

PSEN2 L143H

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: None
Reference Assembly: GRCh37/hg19
Position: Chr1:227073310 T>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CTC to CAC
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 6

Findings

This variant was found in a cognitively healthy African individual from the Bantu population (Guerreiro et al., 2010). It is absent from the gnomAD variant database (v2.1.1, Nov 2021). 

Neuropathology

Not applicable.

Biological Effect

The biological effect of this variant is unknown, but in silico analyses (SIFT, PolyPhen) predicted a damaging effect (Hsu et al., 2020). Consistently, its PHRED-scaled CADD was 25.5, greater than the commonly used threshold of 20 for predicting deleteriousness (CADD v.1.6, Nov 2021). However, the variant alters a residue that is not conserved between PSEN1 and PSEN2 (A137 in PSEN1) located in the second transmembrane domain of the protein. Both Guerreiro et al. and Hsu et al. suggested it could be a benign polymorphism.

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. . 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.
  2. . Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiol Dis. 2020 Jun;139:104817. Epub 2020 Feb 19 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . 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.

Alzpedia

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.