NM_000179.3(MSH6):c.764_765delinsGA (p.Glu255Gly) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 3, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001875935.4

Allele description [Variation Report for NM_000179.3(MSH6):c.764_765delinsGA (p.Glu255Gly)]

NM_000179.3(MSH6):c.764_765delinsGA (p.Glu255Gly)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.764_765delinsGA (p.Glu255Gly)

HGVS:

NC_000002.12:g.47798747_47798748delinsGA
NG_007111.1:g.20601_20602delinsGA
NM_000179.3:c.764_765delinsGAMANE SELECT
NM_001281492.2:c.374_375delinsGA
NM_001281493.2:c.-143_-142delinsGA
NM_001281494.2:c.-143_-142delinsGA
NP_000170.1:p.Glu255Gly
NP_001268421.1:p.Glu125Gly
LRG_219t1:c.764_765delinsGA
LRG_219:g.20601_20602delinsGA
NC_000002.11:g.48025886_48025887delinsGA
NC_000002.11:g.48025886_48025887delinsGA
NM_000179.2:c.764_765delAGinsGA
NM_000179.2:c.764_765delinsGA

Protein change:

E125G

Links:

dbSNP: rs1669253958

NCBI 1000 Genomes Browser:

rs1669253958

Molecular consequence:

NM_001281493.2:c.-143_-142delinsGA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-143_-142delinsGA - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.764_765delinsGA - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.374_375delinsGA - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002250823	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002250823

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002250823.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 920593). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 255 of the MSH6 protein (p.Glu255Gly).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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