NM_005359.6(SMAD4):c.1249_1250del (p.Glu417fs) AND Generalized juvenile polyposis/juvenile polyposis coli

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 5, 2018
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:: RCV000809627.1

Allele description

NM_005359.6(SMAD4):c.1249_1250del (p.Glu417fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.1249_1250del (p.Glu417fs)

HGVS:

NC_000018.10:g.51067126GA[1]
NG_013013.2:g.104087GA[1]
NM_005359.6:c.1249_1250delMANE SELECT
NP_005350.1:p.Glu417fs
LRG_318:g.104087GA[1]
NC_000018.9:g.48593496GA[1]
NM_005359.5:c.1249_1250delGA

Protein change:

E417fs

Links:

dbSNP: rs1599197105

NCBI 1000 Genomes Browser:

rs1599197105

Molecular consequence:

NM_005359.6:c.1249_1250del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Generalized juvenile polyposis/juvenile polyposis coli
Synonyms:: Juvenile polyposis coli
Identifiers:: MONDO: MONDO:0008276; MedGen: C1868081; Orphanet: 329971

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000949790	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 5, 2018)	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

SCV000949790

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 5, 2018)

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000949790.1

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

Description

This sequence change creates a premature translational stop signal (p.Glu417Serfs*11) in the SMAD4 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SMAD4-related disease. Loss-of-function variants in SMAD4 are known to be pathogenic (PMID: 16152648, 16436638, 22810475). 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: Apr 23, 2022

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