3-184163454-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004423.4(DVL3):c.162-203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 152,232 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.026 (65 hom., cov: 31)
• Consequence: DVL3 NM_004423.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

Genes affected

DVL3 (HGNC:3087): (dishevelled segment polarity protein 3) This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila dishevelled gene encodes a cytoplasmic phosphoprotein that regulates cell proliferation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-184163454-A-G is Benign according to our data. Variant chr3-184163454-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219993.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0255 (3885/152232) while in subpopulation NFE AF= 0.0312 (2124/67992). AF 95% confidence interval is 0.0301. There are 65 homozygotes in gnomad4. There are 1851 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 3887 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DVL3	NM_004423.4	c.162-203A>G		intron_variant		ENST00000313143.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DVL3	ENST00000313143.9	c.162-203A>G		intron_variant		1	NM_004423.4	P1

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3887 AN: 152114 Hom.: 65 Cov.: 31

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0770

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0316

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0255 AC: 3885 AN: 152232 Hom.: 65 Cov.: 31 AF XY: 0.0249 AC XY: 1851 AN XY: 74446

Gnomad4 AFR AF: 0.0195

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.0770

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0268 Hom.: 11

Bravo AF: 0.0268

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.9
Dann	Benign	0.87

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: rs138493584; hg19: chr3-183881242;