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NM_005359.6(SMAD4):c.1515del (p.Phe505fs) AND Generalized juvenile polyposis/juvenile polyposis coli

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 8, 2015
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:
RCV000205617.1

Allele description

NM_005359.6(SMAD4):c.1515del (p.Phe505fs)

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.1515del (p.Phe505fs)
HGVS:
  • NC_000018.10:g.51078323del
  • NC_000018.9:g.48604690del
  • NG_013013.2:g.115284del
  • NM_005359.6:c.1515delMANE SELECT
  • NP_005350.1:p.Phe505fs
  • LRG_318:g.115284del
  • NC_000018.9:g.48604690del
  • NC_000018.9:g.48604690delT
  • NC_000018.9:g.48604693del
  • NM_005359.5:c.1512delT
Protein change:
F505fs
Links:
dbSNP: rs864622252
NCBI 1000 Genomes Browser:
rs864622252
Molecular consequence:
  • NM_005359.6:c.1515del - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000259859Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Aug 8, 2015) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000259859.2

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

Description

This sequence change deletes 1 nucleotide from exon 12 of the SMAD4 mRNA (c.1512delT), causing a frameshift at codon 505. This creates a premature translational stop signal in the last exon of the SMAD4 mRNA (p.Phe505Leufs*2). While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated SMAD4 protein. While this particular sequence change has not been reported in the literature, truncating sequence changes in SMAD4 are known to be pathogenic (PMID: 22810475, 16152648). For these reasons, this variant has been classified as Likely Pathogenic.

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

Last Updated: Mar 5, 2024