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NM_000251.3(MSH2):c.2123T>A (p.Ile708Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 27, 2020
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:
RCV002417652.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2123T>A (p.Ile708Asn)]

NM_000251.3(MSH2):c.2123T>A (p.Ile708Asn)

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.2123T>A (p.Ile708Asn)
HGVS:
  • NC_000002.12:g.47476484T>A
  • NG_007110.2:g.78361T>A
  • NM_000251.3:c.2123T>AMANE SELECT
  • NM_001258281.1:c.1925T>A
  • NP_000242.1:p.Ile708Asn
  • NP_001245210.1:p.Ile642Asn
  • LRG_218:g.78361T>A
  • NC_000002.11:g.47703623T>A
  • NM_000251.1:c.2123T>A
Protein change:
I642N
Links:
dbSNP: rs63750108
NCBI 1000 Genomes Browser:
rs63750108
Molecular consequence:
  • NM_000251.3:c.2123T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.1925T>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
SCV002729935Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Aug 27, 2020) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Aberrant splicing in MLH1 and MSH2 due to exonic and intronic variants.

Pagenstecher C, Wehner M, Friedl W, Rahner N, Aretz S, Friedrichs N, Sengteller M, Henn W, Buettner R, Propping P, Mangold E.

Hum Genet. 2006 Mar;119(1-2):9-22. Epub 2005 Dec 8.

PubMed [citation]
PMID:
16341550

Details of each submission

From Ambry Genetics, SCV002729935.2

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

Description

The p.I708N variant (also known as c.2123T>A), located in coding exon 13 of the MSH2 gene, results from a T to A substitution at nucleotide position 2123. The isoleucine at codon 708 is replaced by asparagine, an amino acid with dissimilar properties. This variant has been reported in a family meeting Bethesda criteria and the proband's tumor showed absent MSH2 on IHC (Pagenstecher C et al. Hum. Genet. 2006 Mar;119:9-22). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis.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