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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004848531	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Oct 27, 2021)	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

SCV004848531

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Oct 27, 2021)

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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	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: Jun 23, 2024

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