19-18868623-CCAT-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5
The NM_001492.6(GDF1):c.1090_1092del(p.Met364del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000705 in 1,419,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
GDF1
NM_001492.6 inframe_deletion
NM_001492.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.14
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 Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a chain Embryonic growth/differentiation factor 1 (size 118) in uniprot entity GDF1_HUMAN there are 7 pathogenic changes around while only 2 benign (78%) in NM_001492.6
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001492.6. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 19-18868623-CCAT-C is Pathogenic according to our data. Variant chr19-18868623-CCAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 522570.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF1 | NM_001492.6 | c.1090_1092del | p.Met364del | inframe_deletion | 8/8 | ENST00000247005.8 | |
CERS1 | NM_021267.5 | c.*1359_*1361del | 3_prime_UTR_variant | 8/8 | ENST00000623882.4 | ||
GDF1 | NM_001387438.1 | c.1090_1092del | p.Met364del | inframe_deletion | 5/5 | ||
CERS1 | NM_001387440.1 | c.*1951_*1953del | 3_prime_UTR_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF1 | ENST00000247005.8 | c.1090_1092del | p.Met364del | inframe_deletion | 8/8 | 1 | NM_001492.6 | P1 | |
CERS1 | ENST00000623882.4 | c.*1359_*1361del | 3_prime_UTR_variant | 8/8 | 1 | NM_021267.5 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 7.05e-7 AC: 1AN: 1419180Hom.: 0 AF XY: 0.00000142 AC XY: 1AN XY: 701970
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Right atrial isomerism Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 18, 2018 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at