NM_001281492.1(MSH6):c.2145dup (p.Glu716Ter) AND Lynch syndrome

Clinical significance:Pathogenic (Last evaluated: Sep 5, 2013)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000074751.2

Allele description [Variation Report for NM_001281492.1(MSH6):c.2145dup (p.Glu716Ter)]

NM_001281492.1(MSH6):c.2145dup (p.Glu716Ter)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_001281492.1(MSH6):c.2145dup (p.Glu716Ter)
HGVS:
  • NC_000002.12:g.47800518dup
  • NG_007111.1:g.22372dup
  • NM_001281492.1:c.2145dup
  • NM_001281493.1:c.1629dup
  • NM_001281494.1:c.1629dup
  • NP_001268421.1:p.Glu716Ter
  • NP_001268422.1:p.Glu544Ter
  • NP_001268423.1:p.Glu544Ter
  • LRG_219t1:c.2535dup
  • LRG_219:g.22372dup
  • LRG_219p1:p.Glu846Ter
  • NC_000002.11:g.48027657dup
  • NM_000179.2:c.2535dupT
Protein change:
E544*
Links:
dbSNP: rs587779241
NCBI 1000 Genomes Browser:
rs587779241
Molecular consequence:
  • NM_001281492.1:c.2145dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.1:c.1629dup - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.1:c.1629dup - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Lynch syndrome
Synonyms:
Familial nonpolyposis colon cancer
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100; OMIM: PS120435

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000107961International Society for Gastrointestinal Hereditary Tumours (InSiGHT)reviewed by expert panel
Pathogenic
(Sep 5, 2013)
germlineresearch

Citation Link,

SCV000695817Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Jun 26, 2017)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Description

SCV000107961

Summary from all submissions

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

Citations

PubMed

MSH6 and PMS2 mutation positive Australian Lynch syndrome families: novel mutations, cancer risk and age of diagnosis of colorectal cancer.

Talseth-Palmer BA, McPhillips M, Groombridge C, Spigelman A, Scott RJ.

Hered Cancer Clin Pract. 2010 May 21;8(1):5. doi: 10.1186/1897-4287-8-5.

PubMed [citation]
PMID:
20487569
PMCID:
PMC2890527

Details of each submission

From International Society for Gastrointestinal Hereditary Tumours (InSiGHT), SCV000107961.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided

Description

Coding sequence variation resulting in a stop codon

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695817.1

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

Description

Variant summary: The MSH6 c.2535dupT (p.Glu846X) variant results in a premature termination codon, predicted to cause a truncated or absent MSH6 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2731C>T, p.Arg911X; c.3013C>T, p.Arg1005X; c.3052_3053delCT, p.Leu1018fsX4). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120004 control chromosomes. The variant was reported in a family that fulfilled the Amsterdam II criteria, however two mutation-positive family members did not have cancer, one of which was above the age of onset. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, based on truncating nature of the variant, and the limited clinical data, this variant is classified as likely pathogenic.

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

Last Updated: Aug 27, 2021

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