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NM_000179.3(MSH6):c.3556+1G>A AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 2, 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:
RCV002451123.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3556+1G>A]

NM_000179.3(MSH6):c.3556+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.3556+1G>A
HGVS:
  • NC_000002.12:g.47805028G>A
  • NG_007111.1:g.26882G>A
  • NG_008397.1:g.105648C>T
  • NM_000179.3:c.3556+1G>AMANE SELECT
  • NM_001281492.2:c.3166+1G>A
  • NM_001281493.2:c.2650+1G>A
  • NM_001281494.2:c.2650+1G>A
  • NM_001406795.1:c.3652+1G>A
  • NM_001406796.1:c.3556+1G>A
  • NM_001406797.1:c.3259+1G>A
  • NM_001406798.1:c.3382+1G>A
  • NM_001406799.1:c.3031+1G>A
  • NM_001406800.1:c.3556+1G>A
  • NM_001406801.1:c.3259+1G>A
  • NM_001406802.1:c.3652+1G>A
  • NM_001406803.1:c.2692+1G>A
  • NM_001406804.1:c.3478+1G>A
  • NM_001406805.1:c.3259+1G>A
  • NM_001406806.1:c.3031+1G>A
  • NM_001406807.1:c.3031+1G>A
  • NM_001406808.1:c.3556+1G>A
  • NM_001406809.1:c.3556+1G>A
  • NM_001406811.1:c.2650+1G>A
  • NM_001406812.1:c.2650+1G>A
  • NM_001406813.1:c.3562+1G>A
  • NM_001406814.1:c.2650+1G>A
  • NM_001406815.1:c.2650+1G>A
  • NM_001406816.1:c.2650+1G>A
  • NM_001406817.1:c.1990+1G>A
  • NM_001406818.1:c.3259+1G>A
  • NM_001406819.1:c.3259+1G>A
  • NM_001406820.1:c.3259+1G>A
  • NM_001406821.1:c.3259+1G>A
  • NM_001406822.1:c.3259+1G>A
  • NM_001406823.1:c.2650+1G>A
  • NM_001406824.1:c.3259+1G>A
  • NM_001406825.1:c.3259+1G>A
  • NM_001406826.1:c.3388+1G>A
  • NM_001406827.1:c.3259+1G>A
  • NM_001406828.1:c.3259+1G>A
  • NM_001406829.1:c.2650+1G>A
  • NM_001406830.1:c.3259+1G>A
  • NM_001406831.1:c.337+1G>A
  • NM_001406832.1:c.403+1G>A
  • NM_001407362.1:c.1501+1G>A
  • LRG_219t1:c.3556+1G>A
  • LRG_219:g.26882G>A
  • NC_000002.11:g.48032167G>A
  • NM_000179.2:c.3556+1G>A
Links:
dbSNP: rs1060502926
NCBI 1000 Genomes Browser:
rs1060502926
Molecular consequence:
  • NM_000179.3:c.3556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281492.2:c.3166+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281493.2:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281494.2:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406795.1:c.3652+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406796.1:c.3556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406797.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406798.1:c.3382+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406799.1:c.3031+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406800.1:c.3556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406801.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406802.1:c.3652+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406803.1:c.2692+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406804.1:c.3478+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406805.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406806.1:c.3031+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406807.1:c.3031+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406808.1:c.3556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406809.1:c.3556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406811.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406812.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406813.1:c.3562+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406814.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406815.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406816.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406817.1:c.1990+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406818.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406819.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406820.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406821.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406822.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406823.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406824.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406825.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406826.1:c.3388+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406827.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406828.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406829.1:c.2650+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406830.1:c.3259+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406831.1:c.337+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406832.1:c.403+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407362.1:c.1501+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
SCV002616556Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 2, 2022) 		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

Multigene panel analysis identified germline mutations of DNA repair genes in breast and ovarian cancer.

Hirotsu Y, Nakagomi H, Sakamoto I, Amemiya K, Oyama T, Mochizuki H, Omata M.

Mol Genet Genomic Med. 2015 Sep;3(5):459-66. doi: 10.1002/mgg3.157. Epub 2015 May 12.

PubMed [citation]
PMID:
26436112
PMCID:
PMC4585454

Details of each submission

From Ambry Genetics, SCV002616556.2

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

Description

The c.3556+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 6 of the MSH6 gene. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Other alterations impacting the same donor site (c.3556+1G>T and c.3556+2T>G) have been shown to have a similar impact on splicing and were identified in probands meeting Amsterdam I/II criteria for Lynch syndrome/HNPCC and/or had loss of MSH6 expression in their tumors by immunohistochemistry (Ambry internal data; Hirotsu Y et al. Mol Genet Genomic Med, 2015 Sep;3:459-66). 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. As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: Oct 26, 2024