NM_005359.6(SMAD4):c.902dup (p.Tyr301Ter) AND Juvenile polyposis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 6, 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:: RCV001953721.4

Allele description [Variation Report for NM_005359.6(SMAD4):c.902dup (p.Tyr301Ter)]

NM_005359.6(SMAD4):c.902dup (p.Tyr301Ter)

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.902dup (p.Tyr301Ter)

HGVS:

NC_000018.10:g.51058454dup
NG_013013.2:g.95415dup
NM_005359.6:c.902dupMANE SELECT
NP_005350.1:p.Tyr301Ter
LRG_318:g.95415dup
NC_000018.9:g.48584823_48584824insA
NC_000018.9:g.48584824dup

Protein change:

Y301*

Links:

dbSNP: rs2144429483

NCBI 1000 Genomes Browser:

rs2144429483

Molecular consequence:

NM_005359.6:c.902dup - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002238358	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 6, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23399955, 16152648, 16436638, 22810475, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002238358

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 6, 2022)

germline

clinical testing

PubMed (5)
[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

Prevalence of germline PTEN, BMPR1A, SMAD4, STK11, and ENG mutations in patients with moderate-load colorectal polyps.

Ngeow J, Heald B, Rybicki LA, Orloff MS, Chen JL, Liu X, Yerian L, Willis J, Lehtonen HJ, Lehtonen R, Mester JL, Moline J, Burke CA, Church J, Aaltonen LA, Eng C.

Gastroenterology. 2013 Jun;144(7):1402-9, 1409.e1-5. doi: 10.1053/j.gastro.2013.02.001. Epub 2013 Feb 8.

PubMed [citation]

PMID:: 23399955
PMCID:: PMC3969031

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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002238358.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of juvenile polyposis syndrome (PMID: 23399955). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr301*) 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).

#	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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