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NM_000251.3(MSH2):c.1838dup (p.Asn613fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 14, 2022
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:
RCV000491996.3

Allele description [Variation Report for NM_000251.3(MSH2):c.1838dup (p.Asn613fs)]

NM_000251.3(MSH2):c.1838dup (p.Asn613fs)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.1838dup (p.Asn613fs)
HGVS:
  • NC_000002.12:g.47475103dup
  • NG_007110.2:g.76980dup
  • NM_000251.3:c.1838dupMANE SELECT
  • NM_001258281.1:c.1640dup
  • NP_000242.1:p.Asn613fs
  • NP_001245210.1:p.Asn547fs
  • LRG_218:g.76980dup
  • NC_000002.11:g.47702239_47702240insA
  • NC_000002.11:g.47702242dup
  • NM_000251.1:c.1838dupA
Protein change:
N547fs
Links:
dbSNP: rs1114167815
NCBI 1000 Genomes Browser:
rs1114167815
Molecular consequence:
  • NM_000251.3:c.1838dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001258281.1:c.1640dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000580453Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Sep 14, 2022) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV000580453.6

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

Description

The c.1838dupA pathogenic mutation, located in coding exon 12 of the MSH2 gene, results from a duplication of A at nucleotide position 1838, causing a translational frameshift with a predicted alternate stop codon (p.N613Kfs*31). This pathogenic mutation has been reported in one HNPCC family that had a strong history of ureter, bladder, and kidney cancers (Geary J et al. Fam Cancer. 2008;7(2):163-72). 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

Last Updated: Sep 29, 2024