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.1277-16T>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA017806

138253 (ClinVar)

Gene: MSH2

Condition: Lynch syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 604f1e83-a642-4f95-a050-a20006385d07

Approved on: 2024-09-19

Published on: 2024-10-11

HGVS expressions

NM_000251.3:c.1277-16T>C

NM_000251.3(MSH2):c.1277-16T>C

NC_000002.12:g.47445532T>C

CM000664.2:g.47445532T>C

NC_000002.11:g.47672671T>C

CM000664.1:g.47672671T>C

NC_000002.10:g.47526175T>C

NG_007110.2:g.47409T>C

ENST00000644900.2:c.1277-16T>C

ENST00000233146.7:c.1277-16T>C

ENST00000543555.6:c.1079-16T>C

ENST00000644092.1:c.1277-16T>C

ENST00000645339.1:c.1277-16T>C

ENST00000645506.1:c.1277-16T>C

ENST00000646415.1:c.1277-16T>C

ENST00000233146.6:c.1277-16T>C

ENST00000406134.5:c.1277-16T>C

ENST00000543555.5:c.1079-16T>C

ENST00000610696.4:c.1277-16T>C

ENST00000613514.4:c.1277-16T>C

ENST00000617333.3:c.*43-16T>C

ENST00000617938.4:c.*249-16T>C

ENST00000621359.2:c.1277-16T>C

NM_000251.2:c.1277-16T>C

NM_001258281.1:c.1079-16T>C

Likely Benign

BS1 BP4

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.1277-16T>C is an intronic variant with no impact on gene or gene product predicted using algorithms (MaxEntScan, NNSplice, SpliceAI) (BP4). The gnomAD filtering allele frequency is 0.00015 and gnomAD v4.1 Grpmax AF is 0.00043, attributing BS1 criteria according to the Maximum Credible Allele Frequency (MCAF) cutoffs for MSH2 (BS1). In summary, this variant meets the criteria to be classified as likely benign for Lynch Syndrome, based on the MMR gene specific ACMG/AMP criteria established by the ClinGen InSiGHT Hereditary Colorectal Cancer/ Polyposis VCEP: BS1 and BP4 (VCEP specifications version 1)

BS1

The gnomAD filtering allele frequency is 0.00015 (gnomAD v4.1 Grpmax AF=0.00043), attributing BS1 criteria according to the Maximum Credible Allele Frequency (MCAF) cutoffs for MSH2

BP4

Intronic variant with no impact on gene or gene product predicted using algorithms (MaxEntScan, NNSplice, SpliceAI)

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.