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NM_000179.3(MSH6):c.3556+2T>G AND Lynch syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 13, 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:
RCV004017924.1

Allele description [Variation Report for NM_000179.3(MSH6):c.3556+2T>G]

NM_000179.3(MSH6):c.3556+2T>G

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+2T>G
HGVS:
  • NC_000002.12:g.47805029T>G
  • NG_007111.1:g.26883T>G
  • NG_008397.1:g.105647A>C
  • NM_000179.3:c.3556+2T>GMANE SELECT
  • NM_001281492.2:c.3166+2T>G
  • NM_001281493.2:c.2650+2T>G
  • NM_001281494.2:c.2650+2T>G
  • NM_001406795.1:c.3652+2T>G
  • NM_001406796.1:c.3556+2T>G
  • NM_001406797.1:c.3259+2T>G
  • NM_001406798.1:c.3382+2T>G
  • NM_001406799.1:c.3031+2T>G
  • NM_001406800.1:c.3556+2T>G
  • NM_001406801.1:c.3259+2T>G
  • NM_001406802.1:c.3652+2T>G
  • NM_001406803.1:c.2692+2T>G
  • NM_001406804.1:c.3478+2T>G
  • NM_001406805.1:c.3259+2T>G
  • NM_001406806.1:c.3031+2T>G
  • NM_001406807.1:c.3031+2T>G
  • NM_001406808.1:c.3556+2T>G
  • NM_001406809.1:c.3556+2T>G
  • NM_001406811.1:c.2650+2T>G
  • NM_001406812.1:c.2650+2T>G
  • NM_001406813.1:c.3562+2T>G
  • NM_001406814.1:c.2650+2T>G
  • NM_001406815.1:c.2650+2T>G
  • NM_001406816.1:c.2650+2T>G
  • NM_001406817.1:c.1990+2T>G
  • NM_001406818.1:c.3259+2T>G
  • NM_001406819.1:c.3259+2T>G
  • NM_001406820.1:c.3259+2T>G
  • NM_001406821.1:c.3259+2T>G
  • NM_001406822.1:c.3259+2T>G
  • NM_001406823.1:c.2650+2T>G
  • NM_001406824.1:c.3259+2T>G
  • NM_001406825.1:c.3259+2T>G
  • NM_001406826.1:c.3388+2T>G
  • NM_001406827.1:c.3259+2T>G
  • NM_001406828.1:c.3259+2T>G
  • NM_001406829.1:c.2650+2T>G
  • NM_001406830.1:c.3259+2T>G
  • NM_001406831.1:c.337+2T>G
  • NM_001406832.1:c.403+2T>G
  • NM_001407362.1:c.1501+2T>G
  • LRG_219t1:c.3556+2T>G
  • LRG_219:g.26883T>G
  • NC_000002.11:g.48032168T>G
  • NM_000179.2:c.3556+2T>G
Molecular consequence:
  • NM_000179.3:c.3556+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281492.2:c.3166+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281493.2:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281494.2:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406795.1:c.3652+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406796.1:c.3556+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406797.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406798.1:c.3382+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406799.1:c.3031+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406800.1:c.3556+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406801.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406802.1:c.3652+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406803.1:c.2692+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406804.1:c.3478+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406805.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406806.1:c.3031+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406807.1:c.3031+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406808.1:c.3556+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406809.1:c.3556+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406811.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406812.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406813.1:c.3562+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406814.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406815.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406816.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406817.1:c.1990+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406818.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406819.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406820.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406821.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406822.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406823.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406824.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406825.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406826.1:c.3388+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406827.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406828.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406829.1:c.2650+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406830.1:c.3259+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406831.1:c.337+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001406832.1:c.403+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407362.1:c.1501+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004848380Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(May 13, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848380.1

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

Description

The c.3556+2T>G variant in MSH6 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Heterozygous loss-of-function of the MSH6 gene is an established disease mechanism in individuals with Lynch syndrome. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome based upon predicted impact to the protein and absence in controls. ACMG/AMP criteria applied: PVS1, PM2.

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

Last Updated: Oct 8, 2024