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NM_000251.3(MSH2):c.2150G>A (p.Ser717Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 20, 2021
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:
RCV001181937.5

Allele description [Variation Report for NM_000251.3(MSH2):c.2150G>A (p.Ser717Asn)]

NM_000251.3(MSH2):c.2150G>A (p.Ser717Asn)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.2150G>A (p.Ser717Asn)
HGVS:
  • NC_000002.12:g.47476511G>A
  • NG_007110.2:g.78388G>A
  • NM_000251.3:c.2150G>AMANE SELECT
  • NM_001258281.1:c.1952G>A
  • NP_000242.1:p.Ser717Asn
  • NP_000242.1:p.Ser717Asn
  • NP_001245210.1:p.Ser651Asn
  • LRG_218t1:c.2150G>A
  • LRG_218:g.78388G>A
  • LRG_218p1:p.Ser717Asn
  • NC_000002.11:g.47703650G>A
  • NM_000251.1:c.2150G>A
  • NM_000251.2:c.2150G>A
Protein change:
S651N
Links:
dbSNP: rs752883472
NCBI 1000 Genomes Browser:
rs752883472
Molecular consequence:
  • NM_000251.3:c.2150G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.1952G>A - 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
SCV001347185Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 15, 2019) 		germlineclinical testing

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

SCV002728048Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Sep 20, 2021) 		germlineclinical testing

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

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

Comparison of Molecular, Clinicopathological, and Pedigree Differences Between Lynch-Like and Lynch Syndromes.

Xu Y, Huang Z, Li C, Zhu C, Zhang Y, Guo T, Liu F, Xu Y.

Front Genet. 2020;11:991. doi: 10.3389/fgene.2020.00991.

PubMed [citation]
PMID:
32973888
PMCID:
PMC7466573

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001347185.2

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

Description

This missense variant replaces serine with asparagine at codon 717 of the MSH2 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251486 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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, SCV002728048.2

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

Description

The p.S717N variant (also known as c.2150G>A), located in coding exon 13 of the MSH2 gene, results from a G to A substitution at nucleotide position 2150. The serine at codon 717 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been identified in a cohort of 139 patients with suspected Lynch syndrome (Xu Y et al. Front Genet, 2020 Aug;11:991). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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: Jun 9, 2024