rs573517540

Variant names:

• chr1-1341659-CCA-C
• rs573517540
• NM_001330311.2:c.605+6_605+7delTG

Your query was ambiguous. Multiple possible variants found:

• chr1-1341659-CCA-C
• chr1-1341659-CCA-CCACA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001330311.2(DVL1):​c.605+6_605+7delTG variant causes a splice 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0850
• Publications: 0 publications found

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]

DVL1 Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High AC in GnomAd4 at 822 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330311.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL1	NM_001330311.2	MANE Select	c.605+6_605+7delTG		splice_region intron	N/A	NP_001317240.1	O14640-1
	DVL1	NM_004421.3		c.605+6_605+7delTG		splice_region intron	N/A	NP_004412.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DVL1	ENST00000378888.10	TSL:5 MANE Select	c.605+6_605+7delTG		splice_region intron	N/A	ENSP00000368166.5	O14640-1
	DVL1	ENST00000378891.9	TSL:1	c.605+6_605+7delTG		splice_region intron	N/A	ENSP00000368169.5	O14640-2
	DVL1	ENST00000874577.1		c.770+6_770+7delTG		splice_region intron	N/A	ENSP00000544636.1

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

GnomAD2 exomes AF: 0.00137 AC: 337 AN: 245932 AF XY: 0.00104

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 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

African (AFR) AF: 0.0210 AC: 700 AN: 33306

American (AMR) AF: 0.00113 AC: 50 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25790

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52046

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5732

European-Non Finnish (NFE) AF: 0.0000254 AC: 28 AN: 1101156

Other (OTH) AF: 0.00121 AC: 72 AN: 59732

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

African (AFR) AF: 0.0188 AC: 780 AN: 41582

American (AMR) AF: 0.00144 AC: 22 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68044

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00387 Hom.: 0

Bravo AF: 0.00631

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs573517540; hg19: chr1-1277039;