NM_005359.6(SMAD4):c.1138del (p.Arg380fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 12, 2022
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:: RCV002323940.9

Allele description [Variation Report for NM_005359.6(SMAD4):c.1138del (p.Arg380fs)]

NM_005359.6(SMAD4):c.1138del (p.Arg380fs)

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.1138del (p.Arg380fs)

HGVS:

NC_000018.10:g.51065605del
NG_013013.2:g.102566del
NM_005359.6:c.1138delMANE SELECT
NP_005350.1:p.Arg380fs
LRG_318:g.102566del
NC_000018.9:g.48591974del
NC_000018.9:g.48591975del
NM_005359.5:c.1138delA

Protein change:

R380fs

Links:

dbSNP: rs1555686506

NCBI 1000 Genomes Browser:

rs1555686506

Molecular consequence:

NM_005359.6:c.1138del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV002606620	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 12, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002606620

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 12, 2022)

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, SCV002606620.2

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

Description

The c.1138delA pathogenic mutation, located in coding exon 8 of the SMAD4 gene, results from a deletion of one nucleotide at nucleotide position 1138, causing a translational frameshift with a predicted alternate stop codon (p.R380Gfs*4). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Nov 3, 2024

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