rs6772197

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000266037.10(DOCK3):​c.746+23984G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,130 control chromosomes in the GnomAD database, including 44,750 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 0.76 ( 44750 hom., cov: 32)

Consequence

DOCK3
ENST00000266037.10 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DOCK3NM_004947.5 linkuse as main transcriptc.746+23984G>A intron_variant ENST00000266037.10 NP_004938.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DOCK3ENST00000266037.10 linkuse as main transcriptc.746+23984G>A intron_variant 1 NM_004947.5 ENSP00000266037 P1

Frequencies

GnomAD3 genomes
AF:
0.759
AC:
115338
AN:
152012
Hom.:
44745
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.643
Gnomad AMI
AF:
0.828
Gnomad AMR
AF:
0.627
Gnomad ASJ
AF:
0.877
Gnomad EAS
AF:
0.605
Gnomad SAS
AF:
0.855
Gnomad FIN
AF:
0.863
Gnomad MID
AF:
0.869
Gnomad NFE
AF:
0.839
Gnomad OTH
AF:
0.789
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.758
AC:
115374
AN:
152130
Hom.:
44750
Cov.:
32
AF XY:
0.758
AC XY:
56348
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.642
Gnomad4 AMR
AF:
0.627
Gnomad4 ASJ
AF:
0.877
Gnomad4 EAS
AF:
0.605
Gnomad4 SAS
AF:
0.855
Gnomad4 FIN
AF:
0.863
Gnomad4 NFE
AF:
0.839
Gnomad4 OTH
AF:
0.788
Alfa
AF:
0.786
Hom.:
6977
Bravo
AF:
0.734
Asia WGS
AF:
0.733
AC:
2545
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
1.6
DANN
Benign
0.39

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.

Other links and lift over

dbSNP: rs6772197; hg19: chr3-51151799; API