NM_000179.3(MSH6):c.3556+3_3556+13del AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 28, 2019
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:: RCV002336221.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3556+3_3556+13del]

NM_000179.3(MSH6):c.3556+3_3556+13del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3556+3_3556+13del

HGVS:

NC_000002.12:g.47805030_47805040del
NG_007111.1:g.26884_26894del
NG_008397.1:g.105638_105648del
NM_000179.3:c.3556+3_3556+13delMANE SELECT
NM_001281492.2:c.3166+3_3166+13del
NM_001281493.2:c.2650+3_2650+13del
NM_001281494.2:c.2650+3_2650+13del
LRG_219t1:c.3556+3_3556+13del
LRG_219:g.26884_26894del
NC_000002.11:g.48032167_48032177del
NC_000002.11:g.48032169_48032179del
NM_000179.2:c.3556+3_3556+13del
NM_000179.2:c.3556+3_3556+13del11

Links:

dbSNP: rs587779269

NCBI 1000 Genomes Browser:

rs587779269

Molecular consequence:

NM_000179.3:c.3556+3_3556+13del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281492.2:c.3166+3_3166+13del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281493.2:c.2650+3_2650+13del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281494.2:c.2650+3_2650+13del - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV002618765	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 28, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20487569, 27064304 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002618765

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 28, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

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

Lynch syndrome mutation spectrum in New South Wales, Australia, including 55 novel mutations.

Sjursen W, McPhillips M, Scott RJ, Talseth-Palmer BA.

Mol Genet Genomic Med. 2016 Mar;4(2):223-31. doi: 10.1002/mgg3.198.

PubMed [citation]

PMID:: 27064304
PMCID:: PMC4799874

Details of each submission

From Ambry Genetics, SCV002618765.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.3556+3_3556+13del11 intronic variant, located in intron 6 of the MSH6 gene, results from a deletion of 11 nucleotides within intron 6 of the MSH6 gene. This alteration was reported in the germline of two patients with endometrial cancer that demonstrated isolated absence of MSH6 staining on immunohistochemistry (Ambry internal data; Talseth-Palmer BA et al. Hered Cancer Clin Pract, 2010 May;8:5). In addition, subsequent RNA analysis by RT-PCR using transformed lymphocytes showed skipping of exon 6 (Sjursen W et al. Mol Genet Genomic Med, 2016 Mar;4:223-31). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). These nucleotide positions are generally well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Sep 29, 2024

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