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NM_001492.6(GDF1):c.681C>A (p.Cys227Ter) AND GDF1-RELATED DISORDERS

Germline classification:
Likely pathogenic (1 submission)
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:
RCV003335019.1

Allele description [Variation Report for NM_001492.6(GDF1):c.681C>A (p.Cys227Ter)]

NM_001492.6(GDF1):c.681C>A (p.Cys227Ter)

Genes:
UPF1:UPF1 RNA helicase and ATPase [Gene - OMIM - HGNC]
CERS1:ceramide synthase 1 [Gene - OMIM - HGNC]
GDF1:growth differentiation factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.11
Genomic location:
Preferred name:
NM_001492.6(GDF1):c.681C>A (p.Cys227Ter)
HGVS:
  • NC_000019.10:g.18869035G>T
  • NG_012070.1:g.32110C>A
  • NG_033056.1:g.32110C>A
  • NM_001387438.1:c.681C>A
  • NM_001387440.1:c.*1542C>A
  • NM_001492.6:c.681C>AMANE SELECT
  • NM_021267.5:c.*950C>AMANE SELECT
  • NP_001374367.1:p.Cys227Ter
  • NP_001483.3:p.Cys227Ter
  • NC_000019.9:g.18979844G>T
  • NM_001492.4:c.681C>A
  • NM_001492.5:c.681C>A
Protein change:
C227*; CYS227TER
Links:
OMIM: 602880.0001; dbSNP: rs121434422
NCBI 1000 Genomes Browser:
rs121434422
Molecular consequence:
  • NM_001387440.1:c.*1542C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_021267.5:c.*950C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001387438.1:c.681C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001492.6:c.681C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
GDF1-RELATED DISORDERS
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004046051Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenicgermlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical 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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV004046051.1

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

Description

This nonsense variant is found in the last exon of GDF1 and is therefore predicted to escape nonsense-mediated mRNA decay (NMD). This variant has been previously reported as a heterozygous change in an individual with transposition of the great arteries (PMID: 17924340), and as a compound heterozygous change in patients with cardiac defects (PMID: 20413652, 28991257), including five siblings with right atrial isomerism, who harbored a frameshift variant on the opposite GDF1 allele; the parent who was heterozygous for the p.Cys227Ter variant was unaffected (PMID: 20413652). Heterozygous loss-of-function mutations in GDF1 are a known mechanism of cardiac defects ranging from tetralogy of Fallot to transposition of the great arteries (PMID: 17924340, 28991257, 23410880). The c.681C>A (p.Cys227Ter) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.05% (13/25686) and thus is presumed to be rare. Based on the available evidence, the c.681C>A (p.Cys227Ter) variant is classified as Likely Pathogenic.

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

Last Updated: Nov 24, 2024