NM_005359.6(SMAD4):c.584dup (p.Tyr195Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 11, 2020
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:: RCV002353334.1

Allele description [Variation Report for NM_005359.6(SMAD4):c.584dup (p.Tyr195Ter)]

NM_005359.6(SMAD4):c.584dup (p.Tyr195Ter)

Gene:

SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.584dup (p.Tyr195Ter)

HGVS:

NC_000018.10:g.51054910dup
NG_013013.2:g.91871dup
NM_001407041.1:c.584dup
NM_001407042.1:c.584dup
NM_001407043.1:c.584dup
NM_005359.6:c.584dupMANE SELECT
NP_001393970.1:p.Tyr195Terfs
NP_001393971.1:p.Tyr195Terfs
NP_001393972.1:p.Tyr195Terfs
NP_005350.1:p.Tyr195Ter
NP_005350.1:p.Tyr195Terfs
LRG_318t1:c.584dup
LRG_318:g.91871dup
LRG_318p1:p.Tyr195Terfs
NC_000018.9:g.48581279_48581280insA
NC_000018.9:g.48581280dup
NM_005359.5:c.584dup
NM_005359.5:c.584dupA
NR_176264.1:n.1184dup
NR_176265.1:n.1122dup

Protein change:

Y195*

Molecular consequence:

NM_001407041.1:c.584dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407042.1:c.584dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407043.1:c.584dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407041.1:c.584dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001407042.1:c.584dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001407043.1:c.584dup - nonsense - [Sequence Ontology: SO:0001587]
NM_005359.6:c.584dup - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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

Recent activity

Clear Turn Off Turn On

2570682[uid] (1)
Taxonomy
txid1423[orgn] AND "strain NRS-1244"[All Fields] (1)
BioSample
Microbe sample from Bacillus subtilis
Microbe sample from Bacillus subtilis

biosample

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002647777	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Feb 11, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002647777

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Feb 11, 2020)

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	1	not provided	not provided	1	not provided	clinical testing

Details of each submission

From Ambry Genetics, SCV002647777.1

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

Description

The c.584dupA pathogenic mutation, located in coding exon 4 of the SMAD4 gene, results from a duplication of A at nucleotide position 584, causing a translational frameshift with a predicted alternate stop codon (p.Y195*). 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	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine