Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000179.3(MSH6):c.107C>T (p.Ala36Val)

CA007963

140779 (ClinVar)

Gene: MSH6
Condition: Lynch syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 50ac31d4-b39c-4856-beb7-c69921131dfd
Approved on: 2024-09-19
Published on: 2024-10-11

HGVS expressions

NM_000179.3:c.107C>T
NM_000179.3(MSH6):c.107C>T (p.Ala36Val)
NC_000002.12:g.47783340C>T
CM000664.2:g.47783340C>T
NC_000002.11:g.48010479C>T
CM000664.1:g.48010479C>T
NC_000002.10:g.47863983C>T
NG_007111.1:g.5194C>T
ENST00000700004.2:c.107C>T
ENST00000699999.1:n.191C>T
ENST00000700000.1:c.107C>T
ENST00000700001.1:n.179C>T
ENST00000700002.1:c.107C>T
ENST00000700003.1:c.107C>T
ENST00000234420.11:c.107C>T
ENST00000540021.6:c.107C>T
ENST00000652107.1:c.-37-7587C>T
ENST00000673637.1:c.-38+109C>T
ENST00000673922.1:n.196C>T
ENST00000234420.9:c.107C>T
ENST00000445503.5:c.107C>T
ENST00000456246.1:c.107C>T
ENST00000493177.1:n.171C>T
ENST00000540021.5:c.107C>T
ENST00000606499.1:c.-37-7587C>T
ENST00000614496.4:c.-630C>T
ENST00000616033.4:c.105C>T
ENST00000622629.4:c.-2990C>T
NM_000179.2:c.107C>T
NM_001281492.1:c.107C>T
NM_001281493.1:c.-630C>T
NM_001281492.2:c.107C>T
NM_001281493.2:c.-630C>T
More

Likely Benign

Met criteria codes 2
BS2 BP4
Not Met criteria codes 1
BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH6 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 MSH6 (NM_000179.3):c.107C>T is a missense variant predicted to cause substitution of Alanine to Valine at amino acid 36 (p.Ala36Val). The prior probability for pathogenicity of this missense variant is 0.04 according to http://priors.hci.utah.edu/PRIORS (BP4). The gnomAD v4.1 Grpmax AF is 0.0001535, not meeting BS1 criteria according to the Maximum Credible Allele Frequency (MCAF) cutoffs for MSH6. Co-occurrence with truncating variant MSH6 c.3202C>T (p.Arg1068*) in a patient with CRC and no signs of CMMR-D (BS2). 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: BS2 and BP4 (VCEP specifications version 1)
Met criteria codes
BS2
Co-occurrence with truncating variant MSH6 c.3202C>T (p.Arg1068*) in a patient; with CRC and no signs of CMMR-D
BP4
Missense variant with MAPP+PolyPhen-2 prior probability for pathogenicity <0.11 (Prior probability = 0.1)
Not Met criteria codes
BS1
Freq gnomAD all non-cancer v2.1.1 = 0.0005888 > 0.00022 but gnomAD v4.1 Grpmax AF = 0.0001535 < 0.00022
Curation History
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