NM_002439.5(MSH3):c.146del (p.Pro49fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 31, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000803335.8

Allele description [Variation Report for NM_002439.5(MSH3):c.146del (p.Pro49fs)]

NM_002439.5(MSH3):c.146del (p.Pro49fs)

Genes:

DHFR:dihydrofolate reductase [Gene - OMIM - HGNC]
MSH3:mutS homolog 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q14.1

Genomic location:

Preferred name:

NM_002439.5(MSH3):c.146del (p.Pro49fs)

HGVS:

NC_000005.10:g.80654873del
NG_016607.2:g.5399del
NG_023304.1:g.5111del
NG_105205.1:g.469del
NG_105205.2:g.496del
NM_000791.4:c.-382delMANE SELECT
NM_001290354.2:c.-488del
NM_001290357.2:c.-382del
NM_002439.5:c.146delMANE SELECT
NP_002430.3:p.Pro49fs
NC_000005.9:g.79950690del
NC_000005.9:g.79950692del
NM_002439.3:c.146delC
NM_002439.4:c.146del
NM_002439.4:c.146delC
NR_110936.2:n.113del

Protein change:

P49fs

Links:

dbSNP: rs1580538168

NCBI 1000 Genomes Browser:

rs1580538168

Molecular consequence:

NM_000791.4:c.-382del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001290354.2:c.-488del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001290357.2:c.-382del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_002439.5:c.146del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_110936.2:n.113del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000943199	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 3, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27476653, 37402566, 28492532
SCV005090636	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000943199

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 3, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005090636

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 31, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis.

Adam R, Spier I, Zhao B, Kloth M, Marquez J, Hinrichsen I, Kirfel J, Tafazzoli A, Horpaopan S, Uhlhaas S, Stienen D, Friedrichs N, Altmüller J, Laner A, Holzapfel S, Peters S, Kayser K, Thiele H, Holinski-Feder E, Marra G, Kristiansen G, Nöthen MM, et al.

Am J Hum Genet. 2016 Aug 4;99(2):337-51. doi: 10.1016/j.ajhg.2016.06.015. Epub 2016 Jul 28.

PubMed [citation]

PMID:: 27476653
PMCID:: PMC4974087

MSH3: a confirmed predisposing gene for adenomatous polyposis.

Villy MC, Masliah-Planchon J, Schnitzler A, Delhomelle H, Buecher B, Filser M, Merchadou K, Golmard L, Melaabi S, Vacher S, Blanluet M, Suybeng V, Corsini C, Dhooge M, Hamzaoui N, Farelly S, Ait Omar A, Benamouzig R, Caumette V, Bahuau M, Cucherousset J, Allory Y, et al.

J Med Genet. 2023 Nov 27;60(12):1198-1205. doi: 10.1136/jmg-2023-109341.

PubMed [citation]

PMID:: 37402566

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000943199.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Pro49Leufs*31) in the MSH3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH3 are known to be pathogenic (PMID: 27476653, 37402566). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 648581). For these reasons, this variant has been classified as 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

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005090636.1

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

#	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

ClinVar

Relating variation to medicine