rs797044836

Variant names:

• chr1-1338107-CG-C
• rs797044836
• NM_001330311.2:c.1583delC

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001330311.2(DVL1):​c.1583delC​(p.Pro528ArgfsTer146) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DVL1 NM_001330311.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2 O:1
• Conservation: PhyloP100: 6.52

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]

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-1338107-CG-C is Pathogenic according to our data. Variant chr1-1338107-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 208046.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-1338107-CG-C is described in Lovd as [Pathogenic]. Variant chr1-1338107-CG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DVL1	NM_001330311.2	c.1583delC	p.Pro528ArgfsTer146	frameshift_variant	Exon 14 of 15	ENST00000378888.10	NP_001317240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DVL1	ENST00000378888.10	c.1583delC	p.Pro528ArgfsTer146	frameshift_variant	Exon 14 of 15	5	NM_001330311.2	ENSP00000368166.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant Robinow syndrome 2 Pathogenic:2 Other:1

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GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Apr 02, 2015

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Mar 26, 2015

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs797044836; hg19: chr1-1273487;