Mutations

PSEN2 A258T

Overview

Pathogenicity: Alzheimer's Disease : Benign
Clinical Phenotype: None
Reference Assembly: GRCh37/hg19
Position: Chr1:227076735 G>A
dbSNP ID: rs148238688
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCC to ACC
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 8

Findings

This variant was detected in a control individual in a study assessing 72 AD cases and 58 controls (Frigerio et al., 2015).  There was no family history of dementia. The age of the mutation carrier was not reported, nor were details regarding his or her cognitive health. Classification as a control was based on a lack of significant AD pathology in the brain. Moreover, in HEX, a database of variants from people age 60 or older who did not have a neurodegenerative disease diagnosis or disease-associated neuropathology at the time of death, it was present with an allele count of one in a total of 954 alleles (Nov 2021).

This variant was also found in the gnomAD database with an allele count of 34 and a global frequency of 0.0001 (v2.1.1, Nov 2021). Most carriers were non-Finnish Europeans.

Neuropathology

Not applicable.

Biological Effect

Unknown. In silico, the A258T variant was predicted to be probably damaging by PolyPhen2 (Frigerio et al., 2015) and 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: 08 Nov 2021

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References

Other Citations

  1. Frigerio et al., 2015

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . On the identification of low allele frequency mosaic mutations in the brains of Alzheimer's disease patients. Alzheimers Dement. 2015 Apr 29; PubMed.

Other mutations at this position

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