U.S. flag

An official website of the United States government

NM_005902.4(SMAD3):c.206+1G>C AND Loeys-Dietz syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 16, 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:
RCV000826214.4

Allele description [Variation Report for NM_005902.4(SMAD3):c.206+1G>C]

NM_005902.4(SMAD3):c.206+1G>C

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.206+1G>C
HGVS:
  • NC_000015.10:g.67066361G>C
  • NG_011990.1:g.5505G>C
  • NG_011990.2:g.5761G>C
  • NG_131368.1:g.302G>C
  • NM_001407011.1:c.206+1G>C
  • NM_001407012.1:c.206+1G>C
  • NM_001407013.1:c.206+1G>C
  • NM_005902.4:c.206+1G>CMANE SELECT
  • NC_000015.9:g.67358699G>C
  • NM_005902.3:c.206+1G>C
Links:
dbSNP: rs770098673
NCBI 1000 Genomes Browser:
rs770098673
Molecular consequence:
  • NM_001407011.1:c.206+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407012.1:c.206+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407013.1:c.206+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_005902.4:c.206+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
2

Condition(s)

Name:
Loeys-Dietz syndrome (LDS)
Identifiers:
MONDO: MONDO:0018954; MedGen: C2697932; OMIM: PS609192

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000967780Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely pathogenic
(Mar 16, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

Novel SMAD3 Mutation in a Patient with Hypoplastic Left Heart Syndrome with Significant Aortic Aneurysm.

Fitzgerald KK, Bhat AM, Conard K, Hyland J, Pizarro C.

Case Rep Genet. 2014;2014:591516. doi: 10.1155/2014/591516. Epub 2014 Mar 3.

PubMed [citation]
PMID:
24711937
PMCID:
PMC3970455

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967780.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The c.206+1G>C variant in SMAD3 has not been previously reported in individuals with clinical features of Loeys-Dietz syndrome type 3 (LDS3) or in large populat ion studies. This variant occurs in the invariant region (+/- 1,2) of the SMAD3 exon 1 splice consensus sequence and is predicted to cause altered splicing lead ing to an abnormal or absent protein. Heterozygous loss of function of the SMAD3 gene has been reported in individuals with LDS3. Although, exon 1 is not includ ed in all SMAD3 transcripts, it is present in the predominant transcript and the re is some evidence to support a role for loss of function variants in exon 1 in individuals with clinical features of LDS3 (Fitzgerald 2014). In summary, altho ugh additional studies are required to fully establish its clinical significance , the c.206+1G>C variant is likely pathogenic. ACMG/AMP criteria applied: PVS1_s trong, PM2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: Jun 10, 2023