NM_005359.6(SMAD4):c.208_215del (p.Lys70fs) AND Juvenile polyposis syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 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:: RCV003597155.2

Allele description [Variation Report for NM_005359.6(SMAD4):c.208_215del (p.Lys70fs)]

NM_005359.6(SMAD4):c.208_215del (p.Lys70fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.208_215del (p.Lys70fs)

HGVS:

NC_000018.10:g.51047254_51047261del
NG_013013.2:g.84215_84222del
NM_001407041.1:c.208_215del
NM_001407042.1:c.208_215del
NM_001407043.1:c.208_215del
NM_005359.6:c.208_215delMANE SELECT
NP_001393970.1:p.Lys70fs
NP_001393971.1:p.Lys70fs
NP_001393972.1:p.Lys70fs
NP_005350.1:p.Lys70Tyrfs
NP_005350.1:p.Lys70fs
LRG_318t1:c.208_215del
LRG_318:g.84215_84222del
LRG_318p1:p.Lys70Tyrfs
NC_000018.9:g.48573622_48573629del
NC_000018.9:g.48573624_48573631del
NM_005359.5:c.208_215delAAATGTGT
NR_176264.1:n.746_753del
NR_176265.1:n.746_753del

Protein change:

K70fs

Molecular consequence:

NM_001407041.1:c.208_215del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407042.1:c.208_215del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407043.1:c.208_215del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005359.6:c.208_215del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_176264.1:n.746_753del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_176265.1:n.746_753del - 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
SCV004335153	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 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

SCV004335153

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 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, SCV004335153.1

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

Description

This sequence change creates a premature translational stop signal (p.Lys70Tyrfs*31) 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 is not present in population databases (gnomAD no frequency). 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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