rs6482989

Positions:

• chr10-127065705-A-G
• chr10-127065705-A-T

Variant summary

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

The NM_001290223.2(DOCK1):​c.2445+3929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 151,978 control chromosomes in the GnomAD database, including 41,690 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 0.74 (41690 hom., cov: 31)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2445+3929A>G		intron_variant		ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2445+3929A>G		intron_variant		1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.2382+3929A>G		intron_variant		1		ENSP00000280333	P1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112368 AN: 151860 Hom.: 41657 Cov.: 31

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.740 AC: 112460 AN: 151978 Hom.: 41690 Cov.: 31 AF XY: 0.743 AC XY: 55206 AN XY: 74262

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.760

Alfa AF: 0.716 Hom.: 36969

Bravo AF: 0.746

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.022
DANN	Benign	0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6482989; hg19: chr10-128863969;