rs2766070

Variant names:

• chr10-127290113-C-T
• rs2766070
• NM_001290223.2:c.3044+32684C>T

Variant summary

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

The NM_001290223.2(DOCK1):​c.3044+32684C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,508 control chromosomes in the GnomAD database, including 26,710 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 0.59 (26710 hom., cov: 30)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.3044+32684C>T		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.3044+32684C>T		intron_variant	Intron 29 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.2981+32684C>T		intron_variant	Intron 29 of 51	1		ENSP00000280333.6
DOCK1	ENST00000484400.5	n.197+32684C>T		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.587 AC: 88876 AN: 151388 Hom.: 26681 Cov.: 30

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.587 AC: 88955 AN: 151508 Hom.: 26710 Cov.: 30 AF XY: 0.586 AC XY: 43351 AN XY: 73982

African (AFR) AF: 0.700 AC: 28944 AN: 41342

American (AMR) AF: 0.591 AC: 9017 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1880 AN: 3464

East Asian (EAS) AF: 0.657 AC: 3367 AN: 5122

South Asian (SAS) AF: 0.398 AC: 1900 AN: 4770

European-Finnish (FIN) AF: 0.554 AC: 5769 AN: 10414

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36391 AN: 67840

Other (OTH) AF: 0.560 AC: 1179 AN: 2106

Alfa AF: 0.538 Hom.: 33976

Bravo AF: 0.595

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2766070; hg19: chr10-129088377;