rs573517540

chr1-1341659-CCA-Cchr1-1341659-CCA-CCACA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001330311.2(DVL1):c.605+6_605+7del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,599,232 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (4 hom., cov: 35)
  • Exomes 𝑓: 0.00059 (6 hom.)
• Consequence: DVL1 NM_001330311.2 splice_donor_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0850

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

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-1341659-CCA-C is Benign according to our data. Variant chr1-1341659-CCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 376849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00539 (822/152380) while in subpopulation AFR AF= 0.0188 (780/41582). AF 95% confidence interval is 0.0177. There are 4 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
• BS2: High AC in GnomAd at 821 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DVL1	NM_001330311.2	c.605+6_605+7del		splice_donor_region_variant, intron_variant		ENST00000378888.10
DVL1	NM_004421.3	c.605+6_605+7del		splice_donor_region_variant, intron_variant
DVL1	XM_005244732.5	c.605+6_605+7del		splice_donor_region_variant, intron_variant
DVL1	XM_005244733.5	c.605+6_605+7del		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DVL1	ENST00000378888.10	c.605+6_605+7del		splice_donor_region_variant, intron_variant		5	NM_001330311.2	P3
DVL1	ENST00000378891.9	c.605+6_605+7del		splice_donor_region_variant, intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 821 AN: 152262 Hom.: 4 Cov.: 35

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00137 AC: 337 AN: 245932 Hom.: 2 AF XY: 0.00104 AC XY: 139 AN XY: 133512

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.000934

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000908

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000593 AC: 858 AN: 1446852 Hom.: 6 AF XY: 0.000508 AC XY: 364 AN XY: 716898

Gnomad4 AFR exome AF: 0.0210

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000254

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.00539 AC: 822 AN: 152380 Hom.: 4 Cov.: 35 AF XY: 0.00503 AC XY: 375 AN XY: 74516

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00387 Hom.: 0

Bravo AF: 0.00631

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 18, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 11, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 07, 2020	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs573517540; hg19: chr1-1277039;