NM_000179.3(MSH6):c.829del (p.Glu277fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 3, 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:: RCV002430307.2

Allele description [Variation Report for NM_000179.3(MSH6):c.829del (p.Glu277fs)]

NM_000179.3(MSH6):c.829del (p.Glu277fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.829del (p.Glu277fs)

HGVS:

NC_000002.12:g.47798812del
NG_007111.1:g.20666del
NM_000179.3:c.829delMANE SELECT
NM_001281492.2:c.439del
NM_001281493.2:c.-78del
NM_001281494.2:c.-78del
NM_001406795.1:c.925delG
NM_001406796.1:c.829delG
NM_001406797.1:c.532delG
NM_001406798.1:c.829delG
NM_001406799.1:c.304delG
NM_001406800.1:c.829delG
NM_001406801.1:c.532delG
NM_001406802.1:c.925delG
NM_001406803.1:c.829delG
NM_001406804.1:c.751delG
NM_001406805.1:c.532delG
NM_001406806.1:c.304delG
NM_001406807.1:c.304delG
NM_001406808.1:c.829delG
NM_001406809.1:c.829delG
NM_001406811.1:c.-78delG
NM_001406812.1:c.-78delG
NM_001406813.1:c.835delG
NM_001406814.1:c.-78delG
NM_001406815.1:c.-78delG
NM_001406816.1:c.-78delG
NM_001406817.1:c.829delG
NM_001406818.1:c.532delG
NM_001406819.1:c.532delG
NM_001406820.1:c.532delG
NM_001406821.1:c.532delG
NM_001406822.1:c.532delG
NM_001406823.1:c.-78delG
NM_001406824.1:c.532delG
NM_001406825.1:c.532delG
NM_001406826.1:c.661delG
NM_001406827.1:c.532delG
NM_001406828.1:c.532delG
NM_001406829.1:c.-78delG
NM_001406830.1:c.532delG
NP_000170.1:p.Glu277Lysfs
NP_000170.1:p.Glu277fs
NP_001268421.1:p.Glu147fs
NP_001393724.1:p.Glu309Lysfs
NP_001393725.1:p.Glu277Lysfs
NP_001393726.1:p.Glu178Lysfs
NP_001393727.1:p.Glu277Lysfs
NP_001393728.1:p.Glu102Lysfs
NP_001393729.1:p.Glu277Lysfs
NP_001393730.1:p.Glu178Lysfs
NP_001393731.1:p.Glu309Lysfs
NP_001393732.1:p.Glu277Lysfs
NP_001393733.1:p.Glu251Lysfs
NP_001393734.1:p.Glu178Lysfs
NP_001393735.1:p.Glu102Lysfs
NP_001393736.1:p.Glu102Lysfs
NP_001393737.1:p.Glu277Lysfs
NP_001393738.1:p.Glu277Lysfs
NP_001393742.1:p.Glu279Lysfs
NP_001393746.1:p.Glu277Lysfs
NP_001393747.1:p.Glu178Lysfs
NP_001393748.1:p.Glu178Lysfs
NP_001393749.1:p.Glu178Lysfs
NP_001393750.1:p.Glu178Lysfs
NP_001393751.1:p.Glu178Lysfs
NP_001393753.1:p.Glu178Lysfs
NP_001393754.1:p.Glu178Lysfs
NP_001393755.1:p.Glu221Lysfs
NP_001393756.1:p.Glu178Lysfs
NP_001393757.1:p.Glu178Lysfs
NP_001393759.1:p.Glu178Lysfs
LRG_219t1:c.829del
LRG_219:g.20666del
LRG_219p1:p.Glu277Lysfs
NC_000002.11:g.48025951del
NM_000179.2:c.829delG
NR_176257.1:n.918delG
NR_176258.1:n.918delG
NR_176259.1:n.918delG
NR_176261.1:n.918delG

Protein change:

E147fs

Molecular consequence:

NM_001281493.2:c.-78del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-78del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.829del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.439del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406795.1:c.925delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406796.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406797.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406798.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406799.1:c.304delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406800.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406801.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406802.1:c.925delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406803.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406804.1:c.751delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406805.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406806.1:c.304delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406807.1:c.304delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406808.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406809.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406813.1:c.835delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406817.1:c.829delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406818.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406819.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406820.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406821.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406822.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406824.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406825.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406826.1:c.661delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406827.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406828.1:c.532delG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406830.1:c.532delG - 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
SCV002679273	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 3, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002679273

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 3, 2021)

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, SCV002679273.2

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

Description

The c.829delG pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 829, causing a translational frameshift with a predicted alternate stop codon (p.E277Kfs*2). This variant has been identified in a proband who met Amsterdam I/II criteria for Lynch syndrome and whose tumor demonstrated high microsatellite instability with loss of MSH6 expression by immunohistochemistry (Ambry internal data). 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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