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NM_005359.6(SMAD4):c.787+2T>C AND Generalized juvenile polyposis/juvenile polyposis coli

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 26, 2019
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:
RCV001056035.3

Allele description [Variation Report for NM_005359.6(SMAD4):c.787+2T>C]

NM_005359.6(SMAD4):c.787+2T>C

Gene:
SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q21.2
Genomic location:
Preferred name:
NM_005359.6(SMAD4):c.787+2T>C
HGVS:
  • NC_000018.10:g.51058246T>C
  • NG_013013.2:g.95207T>C
  • NM_001407041.1:c.787+2T>C
  • NM_001407042.1:c.787+2T>C
  • NM_001407043.1:c.787+2T>C
  • NM_005359.6:c.787+2T>CMANE SELECT
  • LRG_318t1:c.787+2T>C
  • LRG_318:g.95207T>C
  • NC_000018.9:g.48584616T>C
  • NM_005359.5:c.787+2T>C
Links:
dbSNP: rs1909895611
NCBI 1000 Genomes Browser:
rs1909895611
Molecular consequence:
  • NM_001407041.1:c.787+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407042.1:c.787+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407043.1:c.787+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_005359.6:c.787+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001363434Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Mar 26, 2019) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363434.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: SMAD4 c.787+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 277066 control chromosomes (gnomAD). To our knowledge, no occurrence of c.787+2T>C in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Feb 20, 2024