NM_000179.3(MSH6):c.3747C>G (p.Tyr1249Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 7, 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:: RCV003176367.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3747C>G (p.Tyr1249Ter)]

NM_000179.3(MSH6):c.3747C>G (p.Tyr1249Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3747C>G (p.Tyr1249Ter)

HGVS:

NC_000002.12:g.47806304C>G
NG_007111.1:g.28158C>G
NG_008397.1:g.104372G>C
NM_000179.3:c.3747C>GMANE SELECT
NM_001281492.2:c.3357C>G
NM_001281493.2:c.2841C>G
NM_001281494.2:c.2841C>G
NM_001406795.1:c.3843C>G
NM_001406796.1:c.3747C>G
NM_001406797.1:c.3450C>G
NM_001406798.1:c.3573C>G
NM_001406799.1:c.3222C>G
NM_001406800.1:c.3747C>G
NM_001406801.1:c.3450C>G
NM_001406802.1:c.3843C>G
NM_001406803.1:c.2883C>G
NM_001406804.1:c.3669C>G
NM_001406805.1:c.3450C>G
NM_001406806.1:c.3222C>G
NM_001406807.1:c.3222C>G
NM_001406808.1:c.3747C>G
NM_001406809.1:c.3747C>G
NM_001406811.1:c.2841C>G
NM_001406812.1:c.2841C>G
NM_001406813.1:c.3753C>G
NM_001406814.1:c.2841C>G
NM_001406815.1:c.2841C>G
NM_001406816.1:c.2841C>G
NM_001406817.1:c.2181C>G
NM_001406818.1:c.3450C>G
NM_001406819.1:c.3450C>G
NM_001406820.1:c.3450C>G
NM_001406821.1:c.3450C>G
NM_001406822.1:c.3450C>G
NM_001406823.1:c.2841C>G
NM_001406824.1:c.3450C>G
NM_001406825.1:c.3450C>G
NM_001406826.1:c.3579C>G
NM_001406827.1:c.3450C>G
NM_001406828.1:c.3450C>G
NM_001406829.1:c.2841C>G
NM_001406830.1:c.3450C>G
NM_001406831.1:c.528C>G
NM_001406832.1:c.594C>G
NM_001407362.1:c.1692C>G
NP_000170.1:p.Tyr1249Ter
NP_000170.1:p.Tyr1249Ter
NP_001268421.1:p.Tyr1119Ter
NP_001268422.1:p.Tyr947Ter
NP_001268423.1:p.Tyr947Ter
NP_001393724.1:p.Tyr1281Ter
NP_001393725.1:p.Tyr1249Ter
NP_001393726.1:p.Tyr1150Ter
NP_001393727.1:p.Tyr1191Ter
NP_001393728.1:p.Tyr1074Ter
NP_001393729.1:p.Tyr1249Ter
NP_001393730.1:p.Tyr1150Ter
NP_001393731.1:p.Tyr1281Ter
NP_001393732.1:p.Tyr961Ter
NP_001393733.1:p.Tyr1223Ter
NP_001393734.1:p.Tyr1150Ter
NP_001393735.1:p.Tyr1074Ter
NP_001393736.1:p.Tyr1074Ter
NP_001393737.1:p.Tyr1249Ter
NP_001393738.1:p.Tyr1249Ter
NP_001393740.1:p.Tyr947Ter
NP_001393741.1:p.Tyr947Ter
NP_001393742.1:p.Tyr1251Ter
NP_001393743.1:p.Tyr947Ter
NP_001393744.1:p.Tyr947Ter
NP_001393745.1:p.Tyr947Ter
NP_001393746.1:p.Tyr727Ter
NP_001393747.1:p.Tyr1150Ter
NP_001393748.1:p.Tyr1150Ter
NP_001393749.1:p.Tyr1150Ter
NP_001393750.1:p.Tyr1150Ter
NP_001393751.1:p.Tyr1150Ter
NP_001393752.1:p.Tyr947Ter
NP_001393753.1:p.Tyr1150Ter
NP_001393754.1:p.Tyr1150Ter
NP_001393755.1:p.Tyr1193Ter
NP_001393756.1:p.Tyr1150Ter
NP_001393757.1:p.Tyr1150Ter
NP_001393758.1:p.Tyr947Ter
NP_001393759.1:p.Tyr1150Ter
NP_001393760.1:p.Tyr176Ter
NP_001393761.1:p.Tyr198Ter
NP_001394291.1:p.Tyr564Ter
LRG_219t1:c.3747C>G
LRG_219:g.28158C>G
LRG_219p1:p.Tyr1249Ter
NC_000002.11:g.48033443C>G
NM_000179.2:c.3747C>G
NR_176256.1:n.2677C>G
NR_176257.1:n.4008C>G
NR_176258.1:n.3937C>G
NR_176259.1:n.3836C>G
NR_176260.1:n.1781C>G
NR_176261.1:n.3718C>G

Protein change:

Y1074*

Molecular consequence:

NR_176256.1:n.2677C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176257.1:n.4008C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176258.1:n.3937C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176259.1:n.3836C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176261.1:n.3718C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000179.3:c.3747C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001281492.2:c.3357C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001281493.2:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001281494.2:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406795.1:c.3843C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406796.1:c.3747C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406797.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406798.1:c.3573C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406799.1:c.3222C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406800.1:c.3747C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406801.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406802.1:c.3843C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406803.1:c.2883C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406804.1:c.3669C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406805.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406806.1:c.3222C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406807.1:c.3222C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406808.1:c.3747C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406809.1:c.3747C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406811.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406812.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406813.1:c.3753C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406814.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406815.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406816.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406817.1:c.2181C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406818.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406819.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406820.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406821.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406822.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406823.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406824.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406825.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406826.1:c.3579C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406827.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406828.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406829.1:c.2841C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406830.1:c.3450C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406831.1:c.528C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001406832.1:c.594C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001407362.1:c.1692C>G - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003855670	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 7, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003855670

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 7, 2022)

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, SCV003855670.2

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

Description

The p.Y1249* pathogenic mutation (also known as c.3747C>G), located in coding exon 8 of the MSH6 gene, results from a C to G substitution at nucleotide position 3747. This changes the amino acid from a tyrosine to a stop codon within coding exon 8. 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

ClinVar

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