10-126999453-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

(HGNC:):

ACMG classification

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/exons	MANE	UniProt
DOCK1	NM_001290223.2	c.849+18T>C		intron_variant		ENST00000623213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2	c.849+18T>C		intron_variant		1	NM_001290223.2
DOCK1	ENST00000280333.9	c.849+18T>C		intron_variant		1		P1
	ENST00000627944.1	n.215+823A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000629917.1	n.201-62A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33031 AN: 151988 Hom.: 3628 Cov.: 32

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

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.: 28 AF XY: 0.212 AC XY: 153417 AN XY: 722722

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.: 32 AF XY: 0.218 AC XY: 16212 AN XY: 74342

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

Other links and lift over

dbSNP: rs2275540; hg19: chr10-128797717; COSMIC: COSV54741267; COSMIC: COSV54741267;