NM_000179.3(MSH6):c.3522_3524delinsAT (p.Phe1174fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 26, 2023
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:: RCV003353056.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3522_3524delinsAT (p.Phe1174fs)]

NM_000179.3(MSH6):c.3522_3524delinsAT (p.Phe1174fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3522_3524delinsAT (p.Phe1174fs)

HGVS:

NC_000002.12:g.47804993_47804995delinsAT
NG_007111.1:g.26847_26849delinsAT
NG_008397.1:g.105681_105683delinsAT
NM_000179.3:c.3522_3524delinsATMANE SELECT
NM_001281492.2:c.3132_3134delinsAT
NM_001281493.2:c.2616_2618delinsAT
NM_001281494.2:c.2616_2618delinsAT
NP_000170.1:p.Phe1174fs
NP_000170.1:p.Phe1174fs
NP_001268421.1:p.Phe1044fs
NP_001268422.1:p.Phe872fs
NP_001268423.1:p.Phe872fs
LRG_219t1:c.3522_3524delinsAT
LRG_219:g.26847_26849delinsAT
LRG_219p1:p.Phe1174fs
NC_000002.11:g.48032132_48032134delinsAT
NM_000179.2:c.3522_3524delTACinsAT
NM_000179.2:c.3522_3524delinsAT

Protein change:

F1044fs

Links:

dbSNP: rs1572738865

NCBI 1000 Genomes Browser:

rs1572738865

Molecular consequence:

NM_000179.3:c.3522_3524delinsAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3132_3134delinsAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.2616_2618delinsAT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.2616_2618delinsAT - 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
SCV004057478	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 26, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004057478

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 26, 2023)

germline

clinical testing

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

Details of each submission

From Ambry Genetics, SCV004057478.2

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

Description

The c.3522_3524delTACinsAT pathogenic mutation, located in coding exon 6 of the MSH6 gene, results from the deletion of 3 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.F1174Lfs*10). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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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