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NM_000179.3(MSH6):c.3438+1G>A AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 27, 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:
RCV002453381.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3438+1G>A]

NM_000179.3(MSH6):c.3438+1G>A

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3438+1G>A
HGVS:
  • NC_000002.12:g.47803686G>A
  • NG_007111.1:g.25540G>A
  • NM_000179.3:c.3438+1G>AMANE SELECT
  • NM_001281492.2:c.3048+1G>A
  • NM_001281493.2:c.2532+1G>A
  • NM_001281494.2:c.2532+1G>A
  • NM_001406795.1:c.3534+1G>A
  • NM_001406796.1:c.3438+1G>A
  • NM_001406797.1:c.3141+1G>A
  • NM_001406798.1:c.3264+1G>A
  • NM_001406799.1:c.2913+1G>A
  • NM_001406800.1:c.3438+1G>A
  • NM_001406801.1:c.3141+1G>A
  • NM_001406802.1:c.3534+1G>A
  • NM_001406803.1:c.2574+1G>A
  • NM_001406804.1:c.3360+1G>A
  • NM_001406805.1:c.3141+1G>A
  • NM_001406806.1:c.2913+1G>A
  • NM_001406807.1:c.2913+1G>A
  • NM_001406808.1:c.3438+1G>A
  • NM_001406809.1:c.3438+1G>A
  • NM_001406811.1:c.2532+1G>A
  • NM_001406812.1:c.2532+1G>A
  • NM_001406813.1:c.3444+1G>A
  • NM_001406814.1:c.2532+1G>A
  • NM_001406815.1:c.2532+1G>A
  • NM_001406816.1:c.2532+1G>A
  • NM_001406817.1:c.1872+1G>A
  • NM_001406818.1:c.3141+1G>A
  • NM_001406819.1:c.3141+1G>A
  • NM_001406820.1:c.3141+1G>A
  • NM_001406821.1:c.3141+1G>A
  • NM_001406822.1:c.3141+1G>A
  • NM_001406823.1:c.2532+1G>A
  • NM_001406824.1:c.3141+1G>A
  • NM_001406825.1:c.3141+1G>A
  • NM_001406826.1:c.3270+1G>A
  • NM_001406827.1:c.3141+1G>A
  • NM_001406828.1:c.3141+1G>A
  • NM_001406829.1:c.2532+1G>A
  • NM_001406830.1:c.3141+1G>A
  • NM_001406831.1:c.219+1G>A
  • NM_001406832.1:c.285+1G>A
  • NM_001407362.1:c.1383+1G>A
  • LRG_219t1:c.3438+1G>A
  • LRG_219:g.25540G>A
  • NC_000002.11:g.48030825G>A
  • NM_000179.2:c.3438+1G>A
Links:
dbSNP: rs267608096
NCBI 1000 Genomes Browser:
rs267608096
Molecular consequence:
  • NM_000179.3:c.3438+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281492.2:c.3048+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281493.2:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281494.2:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406795.1:c.3534+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406796.1:c.3438+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406797.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406798.1:c.3264+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406799.1:c.2913+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406800.1:c.3438+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406801.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406802.1:c.3534+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406803.1:c.2574+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406804.1:c.3360+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406805.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406806.1:c.2913+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406807.1:c.2913+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406808.1:c.3438+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406809.1:c.3438+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406811.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406812.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406813.1:c.3444+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406814.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406815.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406816.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406817.1:c.1872+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406818.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406819.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406820.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406821.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406822.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406823.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406824.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406825.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406826.1:c.3270+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406827.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406828.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406829.1:c.2532+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406830.1:c.3141+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406831.1:c.219+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406832.1:c.285+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407362.1:c.1383+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV002615189Ambry Genetics
criteria provided, single submitter

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

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer.

Overbeek LI, Kets CM, Hebeda KM, Bodmer D, van der Looij E, Willems R, Goossens M, Arts N, Brunner HG, van Krieken JH, Hoogerbrugge N, Ligtenberg MJ.

Br J Cancer. 2007 May 21;96(10):1605-12. Epub 2007 Apr 24.

PubMed [citation]
PMID:
17453009
PMCID:
PMC2359954

Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses.

van der Klift HM, Jansen AM, van der Steenstraten N, Bik EC, Tops CM, Devilee P, Wijnen JT.

Mol Genet Genomic Med. 2015 Jul;3(4):327-45. doi: 10.1002/mgg3.145. Epub 2015 Apr 23.

PubMed [citation]
PMID:
26247049
PMCID:
PMC4521968

Details of each submission

From Ambry Genetics, SCV002615189.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.3438+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 5 of the MSH6 gene. This variant has been reported in an individual with MSI-H rectal cancer diagnosed at age 45 and meeting Amsterdam criteria. It was also reported in an individual diagnosed with MSI-H colon cancer at ag 43, ovarian cancer at age 43, and endometrial cancer at age 53 (Overbeek LI et al. Br J Cancer, 2007 May;96:1605-12). This variant was shown by minigene assay to result in out of frame skipping of exon 5 (van der Klift HM et al. Mol Genet Genomic Med, 2015 Jul;3:327-45). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 8, 2024