10-127024717-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001290223.2(DOCK1):c.1485G>A(p.Ala495=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,612,312 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (15 hom.)
• Consequence: DOCK1 NM_001290223.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.77

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-127024717-G-A is Benign according to our data. Variant chr10-127024717-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640959.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.77 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK1	NM_001290223.2	c.1485G>A	p.Ala495=	synonymous_variant	15/52	ENST00000623213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2	c.1485G>A	p.Ala495=	synonymous_variant	15/52	1	NM_001290223.2
	ENST00000420941.2	n.204+1555C>T		intron_variant, non_coding_transcript_variant		3
	ENST00000601242.5	n.151+1555C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00239 AC: 363 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00390

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00261 AC: 645 AN: 246680 Hom.: 2 AF XY: 0.00282 AC XY: 377 AN XY: 133642

Gnomad AFR exome AF: 0.000329

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00270

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00215

Gnomad FIN exome AF: 0.000885

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00233

GnomAD4 exome AF: 0.00327 AC: 4774 AN: 1460062 Hom.: 15 Cov.: 30 AF XY: 0.00325 AC XY: 2359 AN XY: 726030

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.00307

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00195

Gnomad4 FIN exome AF: 0.000900

Gnomad4 NFE exome AF: 0.00371

Gnomad4 OTH exome AF: 0.00363

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74438

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000943

Gnomad4 NFE AF: 0.00390

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00376 Hom.: 2

Bravo AF: 0.00266

Asia WGS AF: 0.000577 AC: 2 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

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

DOCK1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	4.7
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11595439; hg19: chr10-128822981;