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NM_000179.3(MSH6):c.3556+3_3556+6del AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 17, 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:
RCV002454891.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3556+3_3556+6del]

NM_000179.3(MSH6):c.3556+3_3556+6del

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3556+3_3556+6del
HGVS:
  • NC_000002.12:g.47805030_47805033del
  • NG_007111.1:g.26884_26887del
  • NG_008397.1:g.105645_105648del
  • NM_000179.3:c.3556+3_3556+6delMANE SELECT
  • NM_001281492.2:c.3166+3_3166+6del
  • NM_001281493.2:c.2650+3_2650+6del
  • NM_001281494.2:c.2650+3_2650+6del
  • LRG_219t1:c.3556+3_3556+6del
  • LRG_219:g.26884_26887del
  • NC_000002.11:g.48032169_48032172del
  • NM_000179.2:c.3556+3_3556+6delGAGT
Molecular consequence:
  • NM_000179.3:c.3556+3_3556+6del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281492.2:c.3166+3_3166+6del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281493.2:c.2650+3_2650+6del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001281494.2:c.2650+3_2650+6del - 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
SCV002617331Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Feb 17, 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, SCV002617331.2

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

Description

The c.3556+3_3556+6delGAGT intronic variant results from a deletion of 4 nucleotides within intron 6 of the MSH6 gene. This alteration has been observed in an individual whose colorectal tumor demonstrated high microsatellite instability and loss of MSH6 expression on immunohistochemistry (IHC) (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Another alteration impacting the same donor site (c.3556+4_3556+8delAGTTT) has been described and results in abnormal splicing in the set of samples tested (Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide region is well conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: May 1, 2024