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NM_000179.3(MSH6):c.3556+2T>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 3, 2021
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:
RCV002339752.2

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:
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
SCV002618764Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Apr 3, 2021) 		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, SCV002618764.2

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

Description

The c.3556+2T>G intronic pathogenic mutation results from a T to G substitution two nucleotides after coding exon 6 in the MSH6 gene. This variant has been identified in an individual whose Lynch syndrome associated tumor demonstrated isolated loss of MSH6 expression by immunohistochemistry and family history met Amsterdam II criteria (Ambry internal data). 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). In addition to the clinical data from our internal cohort, 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 8, 2024