U.S. flag

An official website of the United States government

NM_000179.3(MSH6):c.3556+1G>T AND Lynch syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 5, 2017
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:
RCV000826201.5

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

NM_000179.3(MSH6):c.3556+1G>T

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

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

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
SCV000967755Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Dec 5, 2017) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not 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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967755.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The c.3556+1G>T variant in MSH6 has been reported in 1 individual with MSH6-asso ciated cancers (Hirotsu 2015) and was absent from large population studies. The c.3556+1G>T variant occurs in the invariant region (+/- 1,2) of the splice conse nsus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In vitro functional studies provide some evidence that this v ariant causes nonsense mediated decay of MSH6 mRNA and microsatellite instabilit y in tumor sample (Hirotsu 2015). Heterozygous loss of function of the MSH6 gene is an established disease mechanism in Lynch syndrome. In addition, this varian t was classified as pathogenic on Aug 10, 2016 by the ClinGen-approved InSiGHT e xpert panel (ClinVar SCV000551216.1). In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal dominant manner. ACMG/AMP Criteria applied: PVS1; PM2; PS3_Moderate, PS4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Oct 8, 2024