rs869025218
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_004423.4(DVL3):c.1716del(p.Ser573ValfsTer95) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
DVL3
NM_004423.4 frameshift, splice_region
NM_004423.4 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.286
Genes affected
DVL3 (HGNC:3087): (dishevelled segment polarity protein 3) This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila dishevelled gene encodes a cytoplasmic phosphoprotein that regulates cell proliferation. [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 exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.202 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-184170319-GC-G is Pathogenic according to our data. Variant chr3-184170319-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 219221.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-184170319-GC-G is described in Lovd as [Pathogenic]. Variant chr3-184170319-GC-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DVL3 | NM_004423.4 | c.1716del | p.Ser573ValfsTer95 | frameshift_variant, splice_region_variant | 15/15 | ENST00000313143.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DVL3 | ENST00000313143.9 | c.1716del | p.Ser573ValfsTer95 | frameshift_variant, splice_region_variant | 15/15 | 1 | NM_004423.4 | P1 | |
DVL3 | ENST00000431765.6 | c.1665del | p.Ser556ValfsTer95 | frameshift_variant, splice_region_variant | 15/15 | 5 | |||
DVL3 | ENST00000478247.1 | n.1716del | splice_region_variant, non_coding_transcript_exon_variant | 13/13 | 5 | ||||
DVL3 | ENST00000649847.1 | c.*646del | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 10/10 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant Robinow syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Dec 01, 2015 | - - |
Autosomal dominant Robinow syndrome 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 04, 2016 | - - |
Autosomal dominant Robinow syndrome 2 Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at