dbSNP rs1179132425: DVL2:p.Gly529Ala (chr17-7226597-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004422.3(DVL2):c.1586G>C(p.Gly529Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,440,090 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G529E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DVL2
NM_004422.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DVL2	NM_004422.3 link	c.1586G>C	p.Gly529Ala	missense_variant	Exon 14 of 15	ENST00000005340.10	NP_004413.1	O14641
DVL2	XM_005256502.3 link	c.1574G>C	p.Gly525Ala	missense_variant	Exon 14 of 15		XP_005256559.1
DVL2	XM_047435518.1 link	c.1280G>C	p.Gly427Ala	missense_variant	Exon 14 of 15		XP_047291474.1
DVL2	XM_047435522.1 link	c.806G>C	p.Gly269Ala	missense_variant	Exon 9 of 10		XP_047291478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DVL2	ENST00000005340.10 link	c.1586G>C	p.Gly529Ala	missense_variant	Exon 14 of 15	1	NM_004422.3	ENSP00000005340.4	O14641
DVL2	ENST00000575458.5 link	c.1568G>C	p.Gly523Ala	missense_variant	Exon 14 of 15	2		ENSP00000459797.1	I3L2N2
DVL2	ENST00000575086.1 link	c.545G>C	p.Gly182Ala	missense_variant	Exon 6 of 7	3		ENSP00000458465.1	I3L0Z8
DVL2	ENST00000576840.5 link	n.*59G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1440090

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716030

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

D;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.28

Sift

Benign

0.064

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.97

D;.

Vest4

0.77

MutPred

0.15

Loss of glycosylation at S528 (P = 0.0737);.;

MVP

0.72

MPC

0.84

ClinPred

0.96

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.40

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over