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NM_005585.5(SMAD6):c.1055_1056insAT (p.Ala353fs) AND Aortic valve disease 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 2, 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:
RCV003533010.2

Allele description [Variation Report for NM_005585.5(SMAD6):c.1055_1056insAT (p.Ala353fs)]

NM_005585.5(SMAD6):c.1055_1056insAT (p.Ala353fs)

Gene:
SMAD6:SMAD family member 6 [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
15q22.31
Genomic location:
Preferred name:
NM_005585.5(SMAD6):c.1055_1056insAT (p.Ala353fs)
HGVS:
  • NC_000015.10:g.66781099_66781100insAT
  • NG_012244.2:g.83764_83765insAT
  • NM_005585.5:c.1055_1056insATMANE SELECT
  • NP_005576.3:p.Ala353fs
  • NC_000015.9:g.67073437_67073438insAT
  • NM_005585.4:c.1055_1056insAT
  • NR_027654.2:n.2210_2211insAT
Protein change:
A353fs
Links:
dbSNP: rs2140681355
NCBI 1000 Genomes Browser:
rs2140681355
Molecular consequence:
  • NM_005585.5:c.1055_1056insAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_027654.2:n.2210_2211insAT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004297625Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Nov 2, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Two locus inheritance of non-syndromic midline craniosynostosis via rare SMAD6 and common BMP2 alleles.

Timberlake AT, Choi J, Zaidi S, Lu Q, Nelson-Williams C, Brooks ED, Bilguvar K, Tikhonova I, Mane S, Yang JF, Sawh-Martinez R, Persing S, Zellner EG, Loring E, Chuang C, Galm A, Hashim PW, Steinbacher DM, DiLuna ML, Duncan CC, Pelphrey KA, Zhao H, et al.

Elife. 2016 Sep 8;5. doi:pii: e20125. 10.7554/eLife.20125.

PubMed [citation]
PMID:
27606499
PMCID:
PMC5045293

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297625.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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 or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1210484). This frameshift has been observed in individual(s) with craniosynostosis (PMID: 27606499). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the SMAD6 gene (p.Ala353Trpfs*187). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 144 amino acid(s) of the SMAD6 protein and extend the protein by 42 additional amino acid residues.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024