chr17-7225408-C-T

Position:

• chr17-7225408-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004422.3(DVL2):​c.*457G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 467,190 control chromosomes in the GnomAD database, including 541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (159 hom., cov: 32)
  • Exomes 𝑓: 0.024 (382 hom.)
• Consequence: DVL2 NM_004422.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.37

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 17-7225408-C-T is Benign according to our data. Variant chr17-7225408-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1195261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DVL2	NM_004422.3	c.*457G>A		3_prime_UTR_variant	15/15	ENST00000005340.10
DVL2	XM_005256502.3	c.*457G>A		3_prime_UTR_variant	15/15
DVL2	XM_047435518.1	c.*457G>A		3_prime_UTR_variant	15/15
DVL2	XM_047435522.1	c.*457G>A		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DVL2	ENST00000005340.10	c.*457G>A		3_prime_UTR_variant	15/15	1	NM_004422.3	P2
DVL2	ENST00000575458.5			downstream_gene_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4688 AN: 152070 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.0301

GnomAD4 exome AF: 0.0241 AC: 7600 AN: 315002 Hom.: 382 Cov.: 3 AF XY: 0.0235 AC XY: 3937 AN XY: 167450

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.0544

Gnomad4 ASJ exome AF: 0.0378

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.0201

Gnomad4 FIN exome AF: 0.0203

Gnomad4 NFE exome AF: 0.00588

Gnomad4 OTH exome AF: 0.0286

GnomAD4 genome AF: 0.0309 AC: 4706 AN: 152188 Hom.: 159 Cov.: 32 AF XY: 0.0338 AC XY: 2517 AN XY: 74384

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.0587

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.00623

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0208 Hom.: 10

Bravo AF: 0.0352

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1054280; hg19: chr17-7128727;