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NM_000251.3(MSH2):c.2319G>C (p.Lys773Asn) AND Lynch syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 13, 2023
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:
RCV004002779.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2319G>C (p.Lys773Asn)]

NM_000251.3(MSH2):c.2319G>C (p.Lys773Asn)

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.2319G>C (p.Lys773Asn)
HGVS:
  • NC_000002.12:g.47478380G>C
  • NG_007110.2:g.80257G>C
  • NM_000251.3:c.2319G>CMANE SELECT
  • NM_001258281.1:c.2121G>C
  • NP_000242.1:p.Lys773Asn
  • NP_000242.1:p.Lys773Asn
  • NP_001245210.1:p.Lys707Asn
  • LRG_218t1:c.2319G>C
  • LRG_218:g.80257G>C
  • LRG_218p1:p.Lys773Asn
  • NC_000002.11:g.47705519G>C
  • NM_000251.1:c.2319G>C
  • NM_000251.2:c.2319G>C
Protein change:
K707N
Links:
dbSNP: rs745528772
NCBI 1000 Genomes Browser:
rs745528772
Molecular consequence:
  • NM_000251.3:c.2319G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.2121G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004825869All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown4not providednot provided108544not providedclinical testing

Citations

PubMed

Integrated case-control and somatic-germline interaction analyses of soft-tissue sarcoma.

Hu F, Yu Y, Chen JS, Hu H, Scheet P, Huff CD.

J Med Genet. 2021 Mar;58(3):145-153. doi: 10.1136/jmedgenet-2019-106814. Epub 2020 May 23.

PubMed [citation]
PMID:
32447321

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 All of Us Research Program, National Institutes of Health, SCV004825869.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces lysine with asparagine at codon 773 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with soft-tissue sarcoma (PMID: 32447321). This variant has been identified in 2/251432 chromosomes 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
1germlineunknown108544not providednot provided4not providednot providednot provided

Last Updated: May 7, 2024