rs2766051

Variant names:

• chr10-127323628-G-A
• rs2766051
• NM_001290223.2:c.3045-15378G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290223.2(DOCK1):​c.3045-15378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,136 control chromosomes in the GnomAD database, including 4,810 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 (4810 hom., cov: 33)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.3045-15378G>A		intron_variant	Intron 29 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.3045-15378G>A		intron_variant	Intron 29 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.2982-15378G>A		intron_variant	Intron 29 of 51	1		ENSP00000280333.6
DOCK1	ENST00000484400.5	n.198-15378G>A		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33123 AN: 152018 Hom.: 4790 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.218 AC: 33201 AN: 152136 Hom.: 4810 Cov.: 33 AF XY: 0.211 AC XY: 15688 AN XY: 74384

African (AFR) AF: 0.422 AC: 17521 AN: 41472

American (AMR) AF: 0.123 AC: 1874 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.183 AC: 941 AN: 5154

South Asian (SAS) AF: 0.161 AC: 778 AN: 4820

European-Finnish (FIN) AF: 0.0931 AC: 988 AN: 10612

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10134 AN: 67996

Other (OTH) AF: 0.199 AC: 420 AN: 2112

Alfa AF: 0.178 Hom.: 1185

Bravo AF: 0.227

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.92
DANN	Benign	0.64
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2766051; hg19: chr10-129121892;