NM_000179.3(MSH6):c.3822dup (p.Cys1275fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 25, 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:: RCV002358396.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3822dup (p.Cys1275fs)]

NM_000179.3(MSH6):c.3822dup (p.Cys1275fs)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3822dup (p.Cys1275fs)

HGVS:

NC_000002.12:g.47806472dup
NG_007111.1:g.28326dup
NG_008397.1:g.104205dup
NM_000179.3:c.3822dupMANE SELECT
NM_001281492.2:c.3432dup
NM_001281493.2:c.2916dup
NM_001281494.2:c.2916dup
NP_000170.1:p.Cys1275fs
NP_001268421.1:p.Cys1145fs
NP_001268422.1:p.Cys973fs
NP_001268423.1:p.Cys973fs
LRG_219:g.28326dup
NC_000002.11:g.48033611dup
NM_000179.2:c.3822dupA

Protein change:

C1145fs

Links:

dbSNP: rs1553333346

NCBI 1000 Genomes Browser:

rs1553333346

Molecular consequence:

NM_000179.3:c.3822dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3432dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.2916dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.2916dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002621589	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 25, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002621589

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 25, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis.

Lo SM, Choi M, Liu J, Jain D, Boot RG, Kallemeijn WW, Aerts JM, Pashankar F, Kupfer GM, Mane S, Lifton RP, Mistry PK.

Blood. 2012 May 17;119(20):4731-40. doi: 10.1182/blood-2011-10-386862. Epub 2012 Apr 4. Erratum in: Blood. 2014 Oct 9;124(15):2469.

PubMed [citation]

PMID:: 22493294
PMCID:: PMC3367875

Details of each submission

From Ambry Genetics, SCV002621589.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The c.3822dupA pathogenic mutation, located in coding exon 9 of the MSH6 gene, results from a duplication of A at nucleotide position 3822, causing a translational frameshift with a predicted alternate stop codon (p.C1275Mfs*2). Two Mexican-American siblings with CMMRD were found to be homozygous for this mutation (Lo SM et al. Blood, 2012 May;119:4731-40). In addition to the clinical data presented in the literature, 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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