NM_005359.6(SMAD4):c.1507_1508insATCC (p.Met503fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 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:: RCV002390017.2

Allele description [Variation Report for NM_005359.6(SMAD4):c.1507_1508insATCC (p.Met503fs)]

NM_005359.6(SMAD4):c.1507_1508insATCC (p.Met503fs)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.1507_1508insATCC (p.Met503fs)

HGVS:

NC_000018.10:g.51078315_51078316insATCC
NG_013013.2:g.115276_115277insATCC
NM_001407041.1:c.1507_1508insATCC
NM_001407042.1:c.1507_1508insATCC
NM_005359.6:c.1507_1508insATCCMANE SELECT
NP_001393970.1:p.Met503Asnfs
NP_001393971.1:p.Met503Asnfs
NP_005350.1:p.Met503Asnfs
NP_005350.1:p.Met503fs
LRG_318t1:c.1507_1508insATCC
LRG_318:g.115276_115277insATCC
LRG_318p1:p.Met503Asnfs
NC_000018.9:g.48604685_48604686insATCC
NM_005359.5:c.1507_1508insATCC
NR_176265.1:n.2158_2159insATCC

Protein change:

M503fs

Molecular consequence:

NM_001407041.1:c.1507_1508insATCC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407042.1:c.1507_1508insATCC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_005359.6:c.1507_1508insATCC - 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
SCV002699445	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 4, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002699445

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 4, 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, SCV002699445.2

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

Description

The c.1507_1508insATCC pathogenic mutation (also known as p.M503NFS*25), located in coding exon 11 of the SMAD4 gene, results from an insertion of 4 nucleotides at position 1507, causing a translational frameshift with a predicted alternate stop codon. This mutation has been previously identified in a family with juvenile polyposis syndrome and a heavy gastric polyp burden (Stadler ZK, et al. J. Clin. Oncol. 2012 Sep; 30(25):e229-32). In addition to the clinical data presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

#	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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