U.S. flag

An official website of the United States government

NM_005359.6(SMAD4):c.1206dup (p.Ser403Ter) AND Juvenile polyposis syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 11, 2016
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:
RCV002229359.14

Allele description [Variation Report for NM_005359.6(SMAD4):c.1206dup (p.Ser403Ter)]

NM_005359.6(SMAD4):c.1206dup (p.Ser403Ter)

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.1206dup (p.Ser403Ter)
HGVS:
  • NC_000018.10:g.51067085dup
  • NG_013013.2:g.104046dup
  • NM_005359.6:c.1206dupMANE SELECT
  • NP_005350.1:p.Ser403Ter
  • LRG_318:g.104046dup
  • NC_000018.9:g.48593453_48593454insT
  • NC_000018.9:g.48593455dup
  • NM_005359.5:c.1206dupT
Protein change:
S403*
Links:
dbSNP: rs878854765
NCBI 1000 Genomes Browser:
rs878854765
Molecular consequence:
  • NM_005359.6:c.1206dup - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000288868Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 11, 2016) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The prevalence of hereditary hemorrhagic telangiectasia in juvenile polyposis syndrome.

O'Malley M, LaGuardia L, Kalady MF, Parambil J, Heald B, Eng C, Church J, Burke CA.

Dis Colon Rectum. 2012 Aug;55(8):886-92. doi: 10.1097/DCR.0b013e31825aad32.

PubMed [citation]
PMID:
22810475

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000288868.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change inserts 1 nucleotide in exon 10 of the SMAD4 mRNA (c.1206dupT), causing a frameshift at codon 403. This creates a premature translational stop signal (p.Ser403*) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 22810475, 16152648). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024