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NM_000179.3(MSH6):c.1176_1178delinsGGAA (p.Asp392fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Apr 17, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000490855.6

Allele description [Variation Report for NM_000179.3(MSH6):c.1176_1178delinsGGAA (p.Asp392fs)]

NM_000179.3(MSH6):c.1176_1178delinsGGAA (p.Asp392fs)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.1176_1178delinsGGAA (p.Asp392fs)
HGVS:
  • NC_000002.12:g.47799159_47799161delinsGGAA
  • NG_007111.1:g.21013_21015delinsGGAA
  • NM_000179.3:c.1176_1178delinsGGAAMANE SELECT
  • NM_001281492.2:c.786_788delinsGGAA
  • NM_001281493.2:c.270_272delinsGGAA
  • NM_001281494.2:c.270_272delinsGGAA
  • NP_000170.1:p.Asp392fs
  • NP_000170.1:p.Asp392fs
  • NP_001268421.1:p.Asp262fs
  • NP_001268422.1:p.Asp90fs
  • NP_001268423.1:p.Asp90fs
  • LRG_219t1:c.1176_1178delinsGGAA
  • LRG_219:g.21013_21015delinsGGAA
  • LRG_219p1:p.Asp392fs
  • NC_000002.11:g.48026298_48026300delinsGGAA
  • NM_000179.2:c.1176_1178delTGCinsGGAA
  • NM_000179.2:c.1176_1178delinsGGAA
Protein change:
D262fs
Links:
dbSNP: rs1114167718
NCBI 1000 Genomes Browser:
rs1114167718
Molecular consequence:
  • NM_000179.3:c.1176_1178delinsGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281492.2:c.786_788delinsGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281493.2:c.270_272delinsGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001281494.2:c.270_272delinsGGAA - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

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
SCV000580170Ambry Genetics
criteria provided, single submitter

(Ambry Autosomal Dominant and X-Linked criteria (10/2015))		Pathogenic
(Jan 23, 2012) 		germlineclinical testing

Citation Link,

SCV000690179Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Apr 17, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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 Ambry Genetics, SCV000580170.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000690179.3

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

Description

This variant replaces 3 nucleotides in exon 4 of the MSH6 gene with 4 new nucleotides, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

Last Updated: Oct 8, 2024