Variant 17-7226521-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004422.3(DVL2):c.1662A>G(p.Gln554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,606,304 control chromosomes in the GnomAD database, including 303,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25339 hom., cov: 32)

Exomes 𝑓: 0.62 ( 278048 hom. )

Consequence

DVL2
NM_004422.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.869

Variant links:

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]

DVL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-7226521-T-C is Benign according to our data. Variant chr17-7226521-T-C is described in ClinVar as [Benign]. Clinvar id is 1243912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.869 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DVL2	NM_004422.3 linkuse as main transcript	c.1662A>G	p.Gln554=	synonymous_variant	14/15	ENST00000005340.10
DVL2	XM_005256502.3 linkuse as main transcript	c.1650A>G	p.Gln550=	synonymous_variant	14/15
DVL2	XM_047435518.1 linkuse as main transcript	c.1356A>G	p.Gln452=	synonymous_variant	14/15
DVL2	XM_047435522.1 linkuse as main transcript	c.882A>G	p.Gln294=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DVL2	ENST00000005340.10 linkuse as main transcript	c.1662A>G	p.Gln554=	synonymous_variant	14/15	1	NM_004422.3	P2
DVL2	ENST00000575458.5 linkuse as main transcript	c.1644A>G	p.Gln548=	synonymous_variant	14/15	2		A2
DVL2	ENST00000575086.1 linkuse as main transcript	c.624A>G	p.Gln208=	synonymous_variant	6/7	3

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86503

AN:

151760

Hom.:

25313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.586

Gnomad EAS

AF:

0.485

Gnomad SAS

AF:

0.646

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.602

GnomAD3 exomes

AF:

0.598

AC:

146128

AN:

244380

Hom.:

44786

AF XY:

0.610

AC XY:

80578

AN XY:

132182

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.592

Gnomad EAS exome

AF:

0.483

Gnomad SAS exome

AF:

0.660

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.643

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.616

AC:

895551

AN:

1454426

Hom.:

278048

Cov.:

AF XY:

0.619

AC XY:

447997

AN XY:

723358

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.597

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.658

Gnomad4 FIN exome

AF:

0.661

Gnomad4 NFE exome

AF:

0.627

Gnomad4 OTH exome

AF:

0.601

GnomAD4 genome

AF:

0.570

AC:

86576

AN:

151878

Hom.:

25339

Cov.:

AF XY:

0.573

AC XY:

42539

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.586

Gnomad4 EAS

AF:

0.484

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.636

Gnomad4 OTH

AF:

0.606

Alfa

AF:

0.606

Hom.:

6036

Bravo

AF:

0.552

Asia WGS

AF:

0.577

AC:

2011

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.5

DANN

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over