chr17-7225357-G-A

Position:

• chr17-7225357-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004422.3(DVL2):​c.*508C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 569,532 control chromosomes in the GnomAD database, including 1,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (1099 hom., cov: 32)
  • Exomes 𝑓: 0.0098 (322 hom.)
• Consequence: DVL2 NM_004422.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.29

Genes affected

DVL2 (HGNC:3086): (dishevelled segment polarity protein 2) This gene encodes a member of the dishevelled (dsh) protein family. The vertebrate dsh proteins have approximately 40% amino acid sequence similarity with Drosophila dsh. This gene encodes a 90-kD protein that undergoes posttranslational phosphorylation to form a 95-kD cytoplasmic protein, which may play a role in the signal transduction pathway mediated by multiple Wnt proteins. The mechanisms of dishevelled function in Wnt signaling are likely to be conserved among metazoans. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 17-7225357-G-A is Benign according to our data. Variant chr17-7225357-G-A is described in ClinVar as [Benign]. Clinvar id is 1268063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DVL2	NM_004422.3	c.*508C>T		3_prime_UTR_variant	15/15	ENST00000005340.10
DVL2	XM_005256502.3	c.*508C>T		3_prime_UTR_variant	15/15
DVL2	XM_047435518.1	c.*508C>T		3_prime_UTR_variant	15/15
DVL2	XM_047435522.1	c.*508C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DVL2	ENST00000005340.10	c.*508C>T		3_prime_UTR_variant	15/15	1	NM_004422.3	P2

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10039 AN: 152116 Hom.: 1092 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.00984 AC: 4106 AN: 417298 Hom.: 322 Cov.: 4 AF XY: 0.00860 AC XY: 1890 AN XY: 219670

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000836

Gnomad4 FIN exome AF: 0.000117

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0662 AC: 10077 AN: 152234 Hom.: 1099 Cov.: 32 AF XY: 0.0637 AC XY: 4744 AN XY: 74442

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.0463

Alfa AF: 0.0445 Hom.: 176

Bravo AF: 0.0748

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.92

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: rs73976749; hg19: chr17-7128676;