Variant 17-7227512-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004422.3(DVL2):c.1255G>T(p.Val419Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DVL2
NM_004422.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.539

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:

DVL2 (HGNC:):

DVL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DVL2	NM_004422.3 linkuse as main transcript	c.1255G>T	p.Val419Phe	missense_variant	12/15	ENST00000005340.10	NP_004413.1	O14641

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DVL2	ENST00000005340.10 linkuse as main transcript	c.1255G>T	p.Val419Phe	missense_variant	12/15	1	NM_004422.3	ENSP00000005340.4		O14641

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251214

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.1255G>T (p.V419F) alteration is located in exon 12 (coding exon 12) of the DVL2 gene. This alteration results from a G to T substitution at nucleotide position 1255, causing the valine (V) at amino acid position 419 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.067

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.015

D;D

Polyphen

0.97

D;.

Vest4

0.54

MutPred

0.28

Loss of glycosylation at T421 (P = 0.0995);.;

MVP

0.69

MPC

0.39

ClinPred

0.77

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.57

gMVP

0.73

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