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NM_000251.3(MSH2):c.70C>T (p.Gln24Ter) AND Lynch syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 27, 2021
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:
RCV004017400.1

Allele description [Variation Report for NM_000251.3(MSH2):c.70C>T (p.Gln24Ter)]

NM_000251.3(MSH2):c.70C>T (p.Gln24Ter)

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.70C>T (p.Gln24Ter)
Other names:
p.Q24*:CAG>TAG
HGVS:
  • NC_000002.12:g.47403261C>T
  • NG_007110.2:g.5138C>T
  • NM_000251.3:c.70C>TMANE SELECT
  • NM_001258281.1:c.-31+86C>T
  • NP_000242.1:p.Gln24Ter
  • NP_000242.1:p.Gln24Ter
  • LRG_218t1:c.70C>T
  • LRG_218:g.5138C>T
  • LRG_218p1:p.Gln24Ter
  • NC_000002.11:g.47630400C>T
  • NM_000251.1:c.70C>T
  • NM_000251.2:c.70C>T
  • p.Gln24Stop
Protein change:
Q24*
Links:
dbSNP: rs587779976
NCBI 1000 Genomes Browser:
rs587779976
Molecular consequence:
  • NM_001258281.1:c.-31+86C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000251.3:c.70C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004848531Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(Oct 27, 2021) 		germlineclinical testing

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

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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848531.1

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

Description

The p.Gln24X variant in MSH2 has been reported in at least 1 individual with an MSH2-associated cancer (Susswein 2016 PMID: 26681312, Carter 2018 PMID: 30322717). It has also been reported by other clinical laboratories in ClinVar (Variation ID: 127652) and has been identified in 0.003% (1/30994) of Latino/Admixed American chromosomes by gnomAD (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 24, which is predicted to lead to a truncated or absent protein. Loss of function of the MSH2 gene is an established disease mechanism in autosomal dominant Lynch syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP Criteria applied: PVS1, PM2_Supporting.

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

Last Updated: Sep 29, 2024