NM_005359.6(SMAD4):c.1244A>G (p.Asp415Gly) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 11, 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:: RCV002391471.2

Allele description [Variation Report for NM_005359.6(SMAD4):c.1244A>G (p.Asp415Gly)]

NM_005359.6(SMAD4):c.1244A>G (p.Asp415Gly)

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.1244A>G (p.Asp415Gly)

HGVS:

NC_000018.10:g.51067123A>G
NG_013013.2:g.104084A>G
NM_001407041.1:c.1244A>G
NM_001407042.1:c.1244A>G
NM_005359.6:c.1244A>GMANE SELECT
NP_001393970.1:p.Asp415Gly
NP_001393971.1:p.Asp415Gly
NP_005350.1:p.Asp415Gly
NP_005350.1:p.Asp415Gly
LRG_318t1:c.1244A>G
LRG_318:g.104084A>G
LRG_318p1:p.Asp415Gly
NC_000018.9:g.48593493A>G
NM_005359.5:c.1244A>G
NR_176265.1:n.1782A>G

Protein change:

D415G

Molecular consequence:

NM_001407041.1:c.1244A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407042.1:c.1244A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005359.6:c.1244A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002671737	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 11, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002671737

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 11, 2015)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV002671737.2

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

Description

The p.D415G variant (also known as c.1244A>G), located in coding exon 9 of the SMAD4 gene, results from an A to G substitution at nucleotide position 1244. The aspartic acid at codon 415 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 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. Since supporting evidence is limited at this time, the clinical significance of p.D415G remains unclear.

#	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: Jun 9, 2024

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