NM_005585.5(SMAD6):c.2T>C (p.Met1Thr) AND Aortic valve disease 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 17, 2024
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:: RCV003533007.2

Allele description [Variation Report for NM_005585.5(SMAD6):c.2T>C (p.Met1Thr)]

NM_005585.5(SMAD6):c.2T>C (p.Met1Thr)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

15q22.31

Genomic location:

Preferred name:

NM_005585.5(SMAD6):c.2T>C (p.Met1Thr)

HGVS:

NC_000015.10:g.66703260T>C
NG_012244.2:g.5925T>C
NM_005585.5:c.2T>CMANE SELECT
NP_005576.3:p.Met1Thr
NC_000015.9:g.66995598T>C
NM_005585.4:c.2T>C
NR_027654.2:n.1025T>C

Protein change:

M1T

Links:

dbSNP: rs1409145798

NCBI 1000 Genomes Browser:

rs1409145798

Molecular consequence:

NM_005585.5:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_005585.5:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_027654.2:n.1025T>C - 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
SCV004280624	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 17, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34953066, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004280624

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 17, 2024)

germline

clinical testing

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

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

A genotype and phenotype analysis of SMAD6 mutant patients with radioulnar synostosis.

Shen F, Yang Y, Li P, Zheng Y, Luo Z, Fu Y, Zhu G, Mei H, Chen S, Zhu Y.

Mol Genet Genomic Med. 2022 Jan;10(1):e1850. doi: 10.1002/mgg3.1850. Epub 2021 Dec 24.

PubMed [citation]

PMID:: 34953066
PMCID:: PMC8801148

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, SCV004280624.1

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

Description

This sequence change affects the initiator methionine of the SMAD6 mRNA. The next in-frame methionine is located at codon 93. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with SMAD6-related conditions (PMID: 34953066). ClinVar contains an entry for this variant (Variation ID: 1174559). 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.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine