NM_000179.3(MSH6):c.3528_3532del (p.Leu1177fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 9, 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:: RCV000491652.4

Allele description [Variation Report for NM_000179.3(MSH6):c.3528_3532del (p.Leu1177fs)]

NM_000179.3(MSH6):c.3528_3532del (p.Leu1177fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3528_3532del (p.Leu1177fs)

HGVS:

NC_000002.12:g.47804999_47805003del
NG_007111.1:g.26853_26857del
NG_008397.1:g.105674_105678del
NM_000179.3:c.3528_3532delMANE SELECT
NM_001281492.2:c.3138_3142del
NM_001281493.2:c.2622_2626del
NM_001281494.2:c.2622_2626del
NP_000170.1:p.Leu1177fs
NP_000170.1:p.Leu1177fs
NP_001268421.1:p.Leu1047fs
NP_001268422.1:p.Leu875fs
NP_001268423.1:p.Leu875fs
LRG_219t1:c.3528_3532del
LRG_219:g.26853_26857del
LRG_219p1:p.Leu1177fs
NC_000002.11:g.48032137_48032141del
NC_000002.11:g.48032138_48032142del
NM_000179.2:c.3528_3532del
NM_000179.2:c.3528_3532delACTTG

Protein change:

L1047fs

Links:

dbSNP: rs863225408

NCBI 1000 Genomes Browser:

rs863225408

Molecular consequence:

NM_000179.3:c.3528_3532del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3138_3142del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.2622_2626del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.2622_2626del - 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
SCV000580315	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 9, 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

SCV000580315

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 9, 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

Risks of Lynch syndrome cancers for MSH6 mutation carriers.

Baglietto L, Lindor NM, Dowty JG, White DM, Wagner A, Gomez Garcia EB, Vriends AH; Dutch Lynch Syndrome Study Group., Cartwright NR, Barnetson RA, Farrington SM, Tenesa A, Hampel H, Buchanan D, Arnold S, Young J, Walsh MD, Jass J, Macrae F, Antill Y, Winship IM, Giles GG, et al.

J Natl Cancer Inst. 2010 Feb 3;102(3):193-201. doi: 10.1093/jnci/djp473. Epub 2009 Dec 22.

PubMed [citation]

PMID:: 20028993
PMCID:: PMC2815724

Details of each submission

From Ambry Genetics, SCV000580315.6

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

Description

The c.3528_3532delACTTG pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from a deletion of 5 nucleotides at nucleotide positions 3528 to 3532, causing a translational frameshift with a predicted alternate stop codon (p.L1177Cfs*9). This alteration has been seen in a family with HNPCC (Baglietto L et al. J. Natl. Cancer Inst. 2010 Feb;102(3):193-201). In addition to the information 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: Oct 8, 2024

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