NM_000179.3(MSH6):c.2269_2270del (p.Thr757fs) AND Hereditary nonpolyposis colon cancer

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 27, 2022
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:: RCV002271474.1

Allele description [Variation Report for NM_000179.3(MSH6):c.2269_2270del (p.Thr757fs)]

NM_000179.3(MSH6):c.2269_2270del (p.Thr757fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.2269_2270del (p.Thr757fs)

HGVS:

NC_000002.12:g.47800252_47800253del
NG_007111.1:g.22106_22107del
NM_000179.3:c.2269_2270delMANE SELECT
NM_001281492.2:c.1879_1880del
NM_001281493.2:c.1363_1364del
NM_001281494.2:c.1363_1364del
NP_000170.1:p.Thr757fs
NP_000170.1:p.Thr757fs
NP_001268421.1:p.Thr627fs
NP_001268422.1:p.Thr455fs
NP_001268423.1:p.Thr455fs
LRG_219t1:c.2269_2270del
LRG_219:g.22106_22107del
LRG_219p1:p.Thr757fs
NC_000002.11:g.48027391_48027392del
NM_000179.2:c.2269_2270del
NM_000179.2:c.2269_2270delAC

Protein change:

T455fs

Links:

dbSNP: rs876661025

NCBI 1000 Genomes Browser:

rs876661025

Molecular consequence:

NM_000179.3:c.2269_2270del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.1879_1880del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.1363_1364del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.1363_1364del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:: Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:: MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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opioid growth factor receptor [Homo sapiens]
opioid growth factor receptor [Homo sapiens]
gi|33286446|ref|NP_031372.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002556192	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jun 27, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002556192

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jun 27, 2022)

germline

clinical testing

Citation Link

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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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002556192.1

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

Description

Variant summary: MSH6 c.2269_2270delAC (p.Thr757ProfsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant allele was found at a frequency of 4e-06 in 251080 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2269_2270delAC in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely 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: Oct 8, 2024

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