Mutations

PSEN2 T18M

Overview

Pathogenicity: Parkinson's Disease : Not Classified
Clinical Phenotype: Parkinson's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227069661 C>T
dbSNP ID: rs143061887
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ACG to ATG
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 4

Findings

This mutation was identified in a German subject of European descent who developed symptoms of Parkinson’s disease at age 62 (Blauwendraat et al., 2015). He presented with typical PD without atypical features or symptoms of AD until at least age 70. No family history of PD was reported.

Six heterozygotes were reported in the gnomAD variant database, five with European ancestry (v2.1.1, Oct 2021).

Neuropathology

Unknown.

Biological Effect

The biological effect of this mutation is unknown. It is predicted to be damaging in silico (Hsu et al., 2020), with a PHRED-scaled CADD score of 25.4 (v.1.6, Oct 2021), but it is not conserved between PSEN1 and PSEN2.

Last Updated: 29 Oct 2021

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

  1. . Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants. Neurobiol Aging. 2016 Jan;37:208.e11-7. Epub 2015 Sep 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. . Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants. Neurobiol Aging. 2016 Jan;37:208.e11-7. Epub 2015 Sep 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.