19-18868618-C-CACCACCATGTCCTCAT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_001492.6(GDF1):c.1082_1097dupATGAGGACATGGTGGT(p.Asp367fs) variant causes a frameshift, stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
GDF1
NM_001492.6 frameshift, stop_gained
NM_001492.6 frameshift, stop_gained
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.87
Genes affected
GDF1 (HGNC:4214): (growth differentiation factor 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]
CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0197 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| GDF1 | NM_001492.6 | c.1082_1097dupATGAGGACATGGTGGT | p.Asp367fs | frameshift_variant, stop_gained | Exon 8 of 8 | ENST00000247005.8 | NP_001483.3 | |
| CERS1 | NM_021267.5 | c.*1351_*1366dupATGAGGACATGGTGGT | 3_prime_UTR_variant | Exon 8 of 8 | ENST00000623882.4 | NP_067090.1 | ||
| GDF1 | NM_001387438.1 | c.1082_1097dupATGAGGACATGGTGGT | p.Asp367fs | frameshift_variant, stop_gained | Exon 5 of 5 | NP_001374367.1 | ||
| CERS1 | NM_001387440.1 | c.*1943_*1958dupATGAGGACATGGTGGT | 3_prime_UTR_variant | Exon 7 of 7 | NP_001374369.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GDF1 | ENST00000247005.8 | c.1082_1097dupATGAGGACATGGTGGT | p.Asp367fs | frameshift_variant, stop_gained | Exon 8 of 8 | 1 | NM_001492.6 | ENSP00000247005.5 | ||
| CERS1 | ENST00000623882 | c.*1351_*1366dupATGAGGACATGGTGGT | 3_prime_UTR_variant | Exon 8 of 8 | 1 | NM_021267.5 | ENSP00000485308.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital heart defects, multiple types, 6;C3178806:Right atrial isomerism Uncertain:1
Jan 23, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.