Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000251.3(MSH2):c.211G>C (p.Gly71Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA020066

142708 (ClinVar)

Gene: MSH2

Condition: Lynch syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 37d6267b-b7c7-4b94-b086-40428da17513

Approved on: 2024-09-19

Published on: 2024-10-11

HGVS expressions

NM_000251.3:c.211G>C

NM_000251.3(MSH2):c.211G>C (p.Gly71Arg)

NC_000002.12:g.47403402G>C

CM000664.2:g.47403402G>C

NC_000002.11:g.47630541G>C

CM000664.1:g.47630541G>C

NC_000002.10:g.47484045G>C

NG_007110.2:g.5279G>C

ENST00000644900.2:c.211G>C

ENST00000233146.7:c.211G>C

ENST00000543555.6:c.13G>C

ENST00000644092.1:c.211G>C

ENST00000645339.1:c.211G>C

ENST00000645506.1:c.211G>C

ENST00000646415.1:c.211G>C

ENST00000233146.6:c.211G>C

ENST00000406134.5:c.211G>C

ENST00000454849.5:c.13G>C

ENST00000543555.5:c.13G>C

ENST00000610696.4:c.211G>C

ENST00000613514.4:c.211G>C

ENST00000617333.3:c.211G>C

ENST00000617938.4:c.211G>C

ENST00000621359.2:c.211G>C

NM_000251.2:c.211G>C

NM_001258281.1:c.13G>C

Pathogenic

PVS1 PM2_Supporting PP4_Strong

BA1 PP1 BS1

Evidence Links 0

Expert Panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH2 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP

The MSH2 (NM_000251.3):c.211G>C variant affects the last G of exon 1. mRNA assays using RNA derived from patient constitutional biological samples indicates that the variant allele results in a splicing aberration (with evidence that the variant allele produces no full-length/reference transcript) leading to a premature stop codon (PVS1). It was identified in 4 CRC/EC tumours showing loss of MSH2/MSH6 expression in >2 families (PP4_strong). It was absent in gnomAD v2.1, v3.1 and v4.1 datasets (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for Lynch Syndrome, based on the MMR gene specific ACMG/AMP criteria established by the ClinGen InSiGHT Hereditary Colorectal Cancer/ Polyposis VCEP: PVS1, PP4_Strong, and PM2_Sup (VCEP specifications version 1).

PVS1

mRNA assay using RNA derived from patient constitutional biological sample indicates that the variant allele results in a splicing aberration (with evidence that the variant allele produces no full-length/reference transcript) leading to a premature stop codon

PM2_Supporting

Absent in gnomAD v2.1, v3.1 and v4.1

PP4_Strong

4 CRC/EC tumours with loss of MSH2/MSH6 expression

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP1

Segregation LR 1,9 (PMID 28577310)

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.