NM_005902.4(SMAD3):c.871+1G>A AND Ascending aortic dissection

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 18, 2019
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:: RCV001027517.2

Allele description [Variation Report for NM_005902.4(SMAD3):c.871+1G>A]

NM_005902.4(SMAD3):c.871+1G>A

Gene:

SMAD3:SMAD family member 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q22.33

Genomic location:

Preferred name:

NM_005902.4(SMAD3):c.871+1G>A

HGVS:

NC_000015.10:g.67181454G>A
NG_011990.1:g.120598G>A
NG_011990.2:g.120854G>A
NM_001145102.2:c.556+1G>A
NM_001145103.2:c.739+1G>A
NM_001145104.2:c.286+1G>A
NM_001407011.1:c.871+1G>A
NM_001407012.1:c.739+1G>A
NM_001407013.1:c.871+1G>A
NM_001407014.1:c.724+1G>A
NM_001407015.1:c.424+1G>A
NM_001407016.1:c.556+1G>A
NM_001407017.1:c.286+1G>A
NM_005902.4:c.871+1G>AMANE SELECT
NC_000015.9:g.67473792G>A
NM_005902.3:c.871+1G>A

Links:

dbSNP: rs1595956832

NCBI 1000 Genomes Browser:

rs1595956832

Molecular consequence:

NM_001145102.2:c.556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001145103.2:c.739+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001145104.2:c.286+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407011.1:c.871+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407012.1:c.739+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407013.1:c.871+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407014.1:c.724+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407015.1:c.424+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407016.1:c.556+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407017.1:c.286+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_005902.4:c.871+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071]

Observations:

Condition(s)

Name:: Ascending aortic dissection
Identifiers:: MedGen: C1836653; Human Phenotype Ontology: HP:0004933

Recent activity

Clear Turn Off Turn On

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
SCV000992602	Cardiovascular Genetics and the Laboratory of Forensic Genetics, Cyprus Institute of Neurology and Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 18, 2019)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000992602

Cardiovascular Genetics and the Laboratory of Forensic Genetics, Cyprus Institute of Neurology and Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 18, 2019)

inherited

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Cypriots	inherited	yes	11	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Cardiovascular Genetics and the Laboratory of Forensic Genetics, Cyprus Institute of Neurology and Genetics, SCV000992602.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Cypriots	10	not provided	not provided	clinical testing	PubMed (1)
2	Cypriots	1	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was identified in 10 individuals but 7 out of 10 were diagnosed with TAA.

Description

The c.871+1G>A in SMAD3 has been reported in two apparently unrelated Cypriot families with autosomal dominant inheritance, segregated with the thoracic aortic aneurysm (TAA) on seven affected individuals and was absent from large population databases. mRNA analysis showed that this mutation (c.871+1G>A) disrupts normal splicing, leading to exon 6 skipping. According to the ACMG guidelines the c.871+1G>A variant can be classified as pathogenic with one Very Strong (PVS1), one Strong (PS3), one Moderate (PM2) and two Supporting (PP1 and PP3) evidences of pathogenicity.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		10	not provided	2	not provided
2	inherited	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine