Genetic Variant DOCK1:c.849+18T>C (chr10-126999453-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001290223.2(DOCK1):c.849+18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,604,738 control chromosomes in the GnomAD database, including 38,128 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 0.22 ( 3626 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34502 hom. )

Consequence

DOCK1
NM_001290223.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

DOCK1 links:

ENSG00000223528 (HGNC:):

ENSG00000223528 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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 rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2 link	c.849+18T>C		intron_variant	Intron 9 of 51	ENST00000623213.2	NP_001277152.2	B2RUU3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DOCK1	ENST00000623213.2 link	c.849+18T>C	intron_variant	Intron 9 of 51	1	NM_001290223.2	ENSP00000485033.1	A0A096LNH6
DOCK1	ENST00000280333.9 link	c.849+18T>C	intron_variant	Intron 9 of 51	1		ENSP00000280333.6	Q14185
ENSG00000223528	ENST00000627944.1 link	n.215+823A>G	intron_variant	Intron 2 of 2	5
ENSG00000223528	ENST00000629917.1 link	n.201-62A>G	intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33031

AN:

151988

Hom.:

3628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.0969

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.240

GnomAD3 exomes

AF:

0.235

AC:

57415

AN:

244438

Hom.:

7174

AF XY:

0.228

AC XY:

30255

AN XY:

132560

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.327

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.219

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.214

AC:

310700

AN:

1452632

Hom.:

34502

Cov.:

AF XY:

0.212

AC XY:

153417

AN XY:

722722

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.217

GnomAD4 genome

AF:

0.217

AC:

33048

AN:

152106

Hom.:

3626

Cov.:

AF XY:

0.218

AC XY:

16212

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.206

Hom.:

3629

Bravo

AF:

0.224

Asia WGS

AF:

0.278

AC:

967

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.018

DANN

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over