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NM_000179.3(MSH6):c.3248A>G (p.Glu1083Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 15, 2020
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001176773.6

Allele description [Variation Report for NM_000179.3(MSH6):c.3248A>G (p.Glu1083Gly)]

NM_000179.3(MSH6):c.3248A>G (p.Glu1083Gly)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3248A>G (p.Glu1083Gly)
HGVS:
  • NC_000002.12:g.47803495A>G
  • NG_007111.1:g.25349A>G
  • NM_000179.3:c.3248A>GMANE SELECT
  • NM_001281492.2:c.2858A>G
  • NM_001281493.2:c.2342A>G
  • NM_001281494.2:c.2342A>G
  • NP_000170.1:p.Glu1083Gly
  • NP_000170.1:p.Glu1083Gly
  • NP_001268421.1:p.Glu953Gly
  • NP_001268422.1:p.Glu781Gly
  • NP_001268423.1:p.Glu781Gly
  • LRG_219t1:c.3248A>G
  • LRG_219:g.25349A>G
  • LRG_219p1:p.Glu1083Gly
  • NC_000002.11:g.48030634A>G
  • NM_000179.2:c.3248A>G
Protein change:
E1083G
Links:
dbSNP: rs1064796068
NCBI 1000 Genomes Browser:
rs1064796068
Molecular consequence:
  • NM_000179.3:c.3248A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.2858A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281493.2:c.2342A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281494.2:c.2342A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001340823Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 15, 2020) 		germlineclinical testing

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

SCV002609818Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Dec 27, 2019) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001340823.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This missense variant replaces glutamic acid with glycine at codon 1083 of the MSH6 protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV002609818.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.E1083G variant (also known as c.3248A>G), located in coding exon 5 of the MSH6 gene, results from an A to G substitution at nucleotide position 3248. The glutamic acid at codon 1083 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024