U.S. flag

An official website of the United States government

NM_000251.3(MSH2):c.528_529del (p.Cys176_Glu177delinsTer) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jul 27, 2022
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:
RCV000220739.8

Allele description [Variation Report for NM_000251.3(MSH2):c.528_529del (p.Cys176_Glu177delinsTer)]

NM_000251.3(MSH2):c.528_529del (p.Cys176_Glu177delinsTer)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.528_529del (p.Cys176_Glu177delinsTer)
HGVS:
  • NC_000002.12:g.47410251TG[2]
  • NG_007110.2:g.12128TG[2]
  • NM_000251.3:c.528_529delMANE SELECT
  • NM_001258281.1:c.330_331del
  • NP_000242.1:p.Cys176_Glu177delinsTer
  • NP_001245210.1:p.Cys110_Glu111delinsTer
  • LRG_218:g.12128TG[2]
  • NC_000002.11:g.47637390TG[2]
  • NC_000002.11:g.47637390_47637391del
  • NM_000251.1:c.528_529del
  • NM_000251.1:c.528_529delTG
  • NM_000251.2:c.528_529delTG
  • NM_000251.3:c.528_529del
  • p.Cys176*
Links:
dbSNP: rs587779164
NCBI 1000 Genomes Browser:
rs587779164
Molecular consequence:
  • NM_000251.3:c.528_529del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001258281.1:c.330_331del - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000278274Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jul 27, 2022) 		germlineclinical testing

Citation Link,

SCV000905220Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 28, 2020) 		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 Ambry Genetics, SCV000278274.8

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

Description

The c.528_529delTG pathogenic mutation (also known as p.C176*), located in coding exon 3 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 528 to 529. This changes the amino acid from a cysteine to a stop codon within coding exon 3. This mutation was reported in a proband from an HNPCC family whose tumor testing showed high microsatellite instability (MSI-H) (Terdiman JP et al. Gastroenterology. 2001 Jan;120(1):21-30). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

From Color Diagnostics, LLC DBA Color Health, SCV000905220.3

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

Description

This variant deletes 2 nucleotides in exon 3 of the MSH2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with Lynch syndrome (PMID: 11208710, 21642682, 26437257, 28874130). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: May 7, 2024