NM_005359.6(SMAD4):c.860dup (p.His287fs) AND Juvenile polyposis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 29, 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:: RCV003763278.2

Allele description [Variation Report for NM_005359.6(SMAD4):c.860dup (p.His287fs)]

NM_005359.6(SMAD4):c.860dup (p.His287fs)

Gene:

SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.860dup (p.His287fs)

HGVS:

NC_000018.10:g.51058412dup
NG_013013.2:g.95373dup
NM_001407041.1:c.860dup
NM_001407042.1:c.860dup
NM_001407043.1:c.860dup
NM_005359.6:c.860dupMANE SELECT
NP_001393970.1:p.His287fs
NP_001393971.1:p.His287fs
NP_001393972.1:p.His287fs
NP_005350.1:p.His287Glnfs
NP_005350.1:p.His287fs
LRG_318t1:c.860dup
LRG_318:g.95373dup
LRG_318p1:p.His287Glnfs
NC_000018.9:g.48584781_48584782insA
NC_000018.9:g.48584782dup
NM_005359.5:c.860dup
NR_176264.1:n.1460dup
NR_176265.1:n.1398dup

Protein change:

H287fs

Molecular consequence:

NM_001407041.1:c.860dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407042.1:c.860dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407043.1:c.860dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005359.6:c.860dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176264.1:n.1460dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176265.1:n.1398dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Juvenile polyposis syndrome (JPS)
Synonyms:: Polyposis juvenile intestinal; Polyposis familial of entire gastrointestinal tract
Identifiers:: MONDO: MONDO:0017380; MedGen: C0345893; Orphanet: 2929; OMIM: 174900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004449444	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 29, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16152648, 16436638, 22810475, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004449444

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 29, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Vessels' morphology in SMAD4 and BMPR1A-related juvenile polyposis.

Handra-Luca A, Condroyer C, de Moncuit C, Tepper M, Fléjou JF, Thomas G, Olschwang S.

Am J Med Genet A. 2005 Oct 1;138A(2):113-7.

PubMed [citation]

PMID:: 16152648

Mutation screening in juvenile polyposis syndrome.

Pyatt RE, Pilarski R, Prior TW.

J Mol Diagn. 2006 Feb;8(1):84-8.

PubMed [citation]

PMID:: 16436638
PMCID:: PMC1867574

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004449444.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His287Glnfs*21) in the SMAD4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 16152648, 16436638, 22810475). This variant has not been reported in the literature in individuals affected with SMAD4-related conditions. 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

Last Updated: Sep 29, 2024

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