rs869025220
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001330311.2(DVL1):c.1598del(p.Pro533LeufsTer141) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
DVL1
NM_001330311.2 frameshift
NM_001330311.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.83
Genes affected
DVL1 (HGNC:3084): (dishevelled segment polarity protein 1) DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. DVL1 is a candidate gene for neuroblastomatous transformation. The Schwartz-Jampel syndrome and Charcot-Marie-Tooth disease type 2A have been mapped to the same region as DVL1. The phenotypes of these diseases may be consistent with defects which might be expected from aberrant expression of a DVL gene during development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-1338092-AG-A is Pathogenic according to our data. Variant chr1-1338092-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 219223.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-1338092-AG-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DVL1 | NM_001330311.2 | c.1598del | p.Pro533LeufsTer141 | frameshift_variant | 14/15 | ENST00000378888.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DVL1 | ENST00000378888.10 | c.1598del | p.Pro533LeufsTer141 | frameshift_variant | 14/15 | 5 | NM_001330311.2 | P3 | |
DVL1 | ENST00000378891.9 | c.1523del | p.Pro508LeufsTer141 | frameshift_variant | 14/15 | 1 | A1 | ||
DVL1 | ENST00000631679.1 | c.629del | p.Pro210LeufsTer41 | frameshift_variant | 7/8 | 5 | |||
DVL1 | ENST00000632445.1 | c.527del | p.Pro176LeufsTer41 | frameshift_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant Robinow syndrome 2 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Dec 01, 2015 | - - |
Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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