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.1563T>C (p.Tyr521=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA018611

90698 (ClinVar)

Gene: MSH2

Condition: Lynch syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 25bd58f7-d392-4a85-b738-d8cc8f4b637b

Approved on: 2024-09-19

Published on: 2024-10-11

HGVS expressions

NM_000251.3:c.1563T>C

NM_000251.3(MSH2):c.1563T>C (p.Tyr521=)

NC_000002.12:g.47466710T>C

CM000664.2:g.47466710T>C

NC_000002.11:g.47693849T>C

CM000664.1:g.47693849T>C

NC_000002.10:g.47547353T>C

NG_007110.2:g.68587T>C

ENST00000644900.2:c.1563T>C

ENST00000233146.7:c.1563T>C

ENST00000543555.6:c.1365T>C

ENST00000644092.1:c.1563T>C

ENST00000645339.1:c.1563T>C

ENST00000645506.1:c.1563T>C

ENST00000646415.1:c.1563T>C

ENST00000233146.6:c.1563T>C

ENST00000406134.5:c.1563T>C

ENST00000543555.5:c.1365T>C

ENST00000610696.4:c.1563T>C

ENST00000613514.4:c.*103T>C

ENST00000617333.3:c.*329T>C

ENST00000617938.4:c.*535T>C

ENST00000621359.2:c.1563T>C

NM_000251.2:c.1563T>C

NM_001258281.1:c.1365T>C

Likely Benign

BS1 BP7 BP4

BP5

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 c.1563T>C variant is a synonymous variant, p.(Tyr521=). It is present in GnomAD v2.1.1 (non-cancer dataset) and gnomAD v4.1 within the Maximum Credible Allele Frequency (MCAF) cutoff 0.0001-0.001 (0.01-0.1%). It is not predicted to affect splicing according to predictions from http://priors.hci.utah.edu/PRIORS and SpliceAI. Therefore, this variant is classified as likely benign. (VCEP specifications version 1)

BS1

Freq gnomAD all non-cancer v2.1.1 = 0.39141%; MCAF 95% = 0.03914%. gnomAD v4 Grpmax AF = 0.0453%

BP7

BP7 is assigned because it is a synonymous variant.

BP4

BP4 is assigned because splicing predictors do not predict any effect (max Splice-AI value= 0.11 and Prior_utah_splicing_de_novo=0.02 ).

BP5

1 CRC showing MSI-L/IHC normal (Ontario CCFR; Insight database)

Curation History

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