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NM_005359.6(SMAD4):c.1529G>T (p.Gly510Val) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 25, 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:
RCV002400831.2

Allele description [Variation Report for NM_005359.6(SMAD4):c.1529G>T (p.Gly510Val)]

NM_005359.6(SMAD4):c.1529G>T (p.Gly510Val)

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.1529G>T (p.Gly510Val)
HGVS:
  • NC_000018.10:g.51078337G>T
  • NG_013013.2:g.115298G>T
  • NM_005359.6:c.1529G>TMANE SELECT
  • NP_005350.1:p.Gly510Val
  • NP_005350.1:p.Gly510Val
  • LRG_318t1:c.1529G>T
  • LRG_318:g.115298G>T
  • LRG_318p1:p.Gly510Val
  • NC_000018.9:g.48604707G>T
  • NM_005359.5:c.1529G>T
Protein change:
G510V
Links:
dbSNP: rs377767371
NCBI 1000 Genomes Browser:
rs377767371
Molecular consequence:
  • NM_005359.6:c.1529G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial thoracic aortic aneurysm and aortic dissection (TAAD)
Synonyms:
Thoracic aortic aneurysm and aortic dissection; Thoracic aortic aneurysms and dissections
Identifiers:
MONDO: MONDO:0019625; MedGen: C4707243; Orphanet: 91387; OMIM: PS607086
Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002705494Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Nov 25, 2015) 		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 Ambry Genetics, SCV002705494.2

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

Description

The p.G510V variant (also known as c.1529G>T), located in coding exon 11 of the SMAD4 gene, results from a G to T substitution at nucleotide position 1529. The glycine at codon 510 is replaced by valine, an amino acid with dissimilar properties. This alteration has been detected in multiple individuals meeting clinical diagnostic criteria for Juvenile Polyposis syndrome (JPS) (Howe, JR et al. J Med Genet. 2004 Jul;41(7):484-91); Calva-Cerqueira, Clin Genet. 2009 Jan;75(1):79-85). This variant was previously reported in the SNPDatabase as rs377767371, but was absent from population-based cohorts in the NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project databases. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65,000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Jun 9, 2024