NM_000179.2(MSH6):c.1740G>T (p.Ser580=) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Aug 21, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000579551.4

Allele description [Variation Report for NM_000179.2(MSH6):c.1740G>T (p.Ser580=)]

NM_000179.2(MSH6):c.1740G>T (p.Ser580=)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.2(MSH6):c.1740G>T (p.Ser580=)
HGVS:
  • NC_000002.12:g.47799723G>T
  • NG_007111.1:g.21577G>T
  • NM_000179.2:c.1740G>T
  • NM_001281492.1:c.1350G>T
  • NM_001281493.1:c.834G>T
  • NM_001281494.1:c.834G>T
  • NP_000170.1:p.Ser580=
  • NP_001268421.1:p.Ser450=
  • NP_001268422.1:p.Ser278=
  • NP_001268423.1:p.Ser278=
  • LRG_219t1:c.1740G>T
  • LRG_219:g.21577G>T
  • LRG_219p1:p.Ser580=
  • NC_000002.11:g.48026862G>T
Links:
dbSNP: rs762089407
NCBI 1000 Genomes Browser:
rs762089407
Molecular consequence:
  • NM_000179.2:c.1740G>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001281492.1:c.1350G>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001281493.1:c.834G>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001281494.1:c.834G>T - synonymous variant - [Sequence Ontology: SO:0001819]
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; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000685224Color Health, Inccriteria provided, single submitter
Uncertain significance
(Aug 21, 2019)
germlineclinical testing

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

SCV001173435Ambry Geneticscriteria provided, single submitter
Likely benign
(Jun 4, 2019)
germlineclinical testing

Citation Link

Description

This synonymous variant does not change the amino acid sequence of the MSH6 protein. Splice site prediction tools suggest that this variant may create a splice acceptor site. However, this prediction has not been confirmed in published RNA studies. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250230 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

SCV000685224

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 Color Health, Inc, SCV000685224.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Ambry Genetics, SCV001173435.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign

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

Last Updated: Feb 3, 2021

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