Variant 17-7226655-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004422.3(DVL2):c.1544-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,506,842 control chromosomes in the GnomAD database, including 284,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25349 hom., cov: 32)

Exomes 𝑓: 0.62 ( 259182 hom. )

Consequence

DVL2
NM_004422.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.442

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-7226655-A-G is Benign according to our data. Variant chr17-7226655-A-G is described in ClinVar as [Benign]. Clinvar id is 1182212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DVL2	NM_004422.3 linkuse as main transcript	c.1544-16T>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000005340.10
DVL2	XM_005256502.3 linkuse as main transcript	c.1532-16T>C	splice_polypyrimidine_tract_variant, intron_variant
DVL2	XM_047435518.1 linkuse as main transcript	c.1238-16T>C	splice_polypyrimidine_tract_variant, intron_variant
DVL2	XM_047435522.1 linkuse as main transcript	c.764-16T>C	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
DVL2	ENST00000005340.10 linkuse as main transcript	c.1544-16T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_004422.3	P2
DVL2	ENST00000575086.1 linkuse as main transcript	c.505-16T>C	splice_polypyrimidine_tract_variant, intron_variant	3
DVL2	ENST00000575458.5 linkuse as main transcript	c.1526-16T>C	splice_polypyrimidine_tract_variant, intron_variant	2		A2
DVL2	ENST00000576840.5 linkuse as main transcript		downstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86525

AN:

151858

Hom.:

25321

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.556

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.603

GnomAD3 exomes

AF:

0.597

AC:

101702

AN:

170374

Hom.:

30654

AF XY:

0.609

AC XY:

56052

AN XY:

92066

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.600

Gnomad EAS exome

AF:

0.483

Gnomad SAS exome

AF:

0.664

Gnomad FIN exome

AF:

0.666

Gnomad NFE exome

AF:

0.646

Gnomad OTH exome

AF:

0.613

GnomAD4 exome

AF:

0.616

AC:

834895

AN:

1354866

Hom.:

259182

Cov.:

AF XY:

0.619

AC XY:

413016

AN XY:

666852

show subpopulations

Gnomad4 AFR exome

AF:

0.429

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.457

Gnomad4 SAS exome

AF:

0.658

Gnomad4 FIN exome

AF:

0.657

Gnomad4 NFE exome

AF:

0.627

Gnomad4 OTH exome

AF:

0.602

GnomAD4 genome

AF:

0.570

AC:

86601

AN:

151976

Hom.:

25349

Cov.:

AF XY:

0.573

AC XY:

42543

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.587

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.646

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.636

Gnomad4 OTH

AF:

0.607

Alfa

AF:

0.625

Hom.:

68824

Bravo

AF:

0.552

Asia WGS

AF:

0.577

AC:

2010

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

-0.82

CADD

Benign

5.5

DANN

Benign

0.47

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