NM_005585.5(SMAD6):c.1412_1413delinsT (p.Gly471fs) AND Aortic valve disease 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 27, 2018
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:: RCV003532235.1

Allele description [Variation Report for NM_005585.5(SMAD6):c.1412_1413delinsT (p.Gly471fs)]

NM_005585.5(SMAD6):c.1412_1413delinsT (p.Gly471fs)

Gene:

SMAD6:SMAD family member 6 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

15q22.31

Genomic location:

Preferred name:

NM_005585.5(SMAD6):c.1412_1413delinsT (p.Gly471fs)

HGVS:

NC_000015.10:g.66781456_66781457delinsT
NG_012244.2:g.84121_84122delinsT
NM_005585.5:c.1412_1413delinsTMANE SELECT
NP_005576.3:p.Gly471fs
NC_000015.9:g.67073794_67073795delinsT
NG_012244.1:g.84121_84122delinsT
NR_027654.2:n.2567_2568delinsT

Protein change:

G471fs

Links:

dbSNP: rs1567116253

NCBI 1000 Genomes Browser:

rs1567116253

Molecular consequence:

NM_005585.5:c.1412_1413delinsT - frameshift variant - [Sequence Ontology: SO:0001589]
NR_027654.2:n.2567_2568delinsT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Aortic valve disease 2 (AOVD2)
Identifiers:: MONDO: MONDO:0013902; MedGen: C3542024; OMIM: 614823

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
SCV000819200	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 27, 2018)	germline	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

SCV000819200

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 27, 2018)

germline

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000819200.2

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

Description

This sequence change results in a frameshift at codon 471 in the last exon of the SMAD6 mRNA (p.Gly471Alafs*68). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acids of the SMAD6 protein, and to extend the protein by an additional 41 amino acids. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SMAD6-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown.

#	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: May 1, 2024

ClinVar

Relating variation to medicine