rs12487468

chr3-51352139-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004947.5(DOCK3):c.4107+1747A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,260 control chromosomes in the GnomAD database, including 947 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.070 (947 hom., cov: 32)
• Consequence: DOCK3 NM_004947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

Genes affected

DOCK3 (HGNC:2989): (dedicator of cytokinesis 3) This gene is specifically expressed in the central nervous system (CNS). It encodes a member of the DOCK (dedicator of cytokinesis) family of guanine nucleotide exchange factors (GEFs). This protein, dedicator of cytokinesis 3 (DOCK3), is also known as modifier of cell adhesion (MOCA) and presenilin-binding protein (PBP). The DOCK3 and DOCK1, -2 and -4 share several conserved amino acids in their DHR-2 (DOCK homology region 2) domains that are required for GEF activity, and bind directly to WAVE proteins [Wiskott-Aldrich syndrome protein (WASP) family Verprolin-homologous proteins] via their DHR-1 domains. The DOCK3 induces axonal outgrowth in CNS by stimulating membrane recruitment of the WAVE complex and activating the small G protein Rac1. This gene is associated with an attention deficit hyperactivity disorder-like phenotype by a complex chromosomal rearrangement. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK3	NM_004947.5	c.4107+1747A>G		intron_variant		ENST00000266037.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK3	ENST00000266037.10	c.4107+1747A>G		intron_variant		1	NM_004947.5	P1

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10706 AN: 152142 Hom.: 945 Cov.: 32

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0703 AC: 10710 AN: 152260 Hom.: 947 Cov.: 32 AF XY: 0.0745 AC XY: 5546 AN XY: 74448

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0307 Hom.: 124

Bravo AF: 0.0878

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	3.9
Dann	Benign	0.86

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: rs12487468; hg19: chr3-51389570;