rs10741150

Variant names:

• chr10-126981694-C-T
• rs10741150
• NM_001290223.2:c.172-224C>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.172-224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,066 control chromosomes in the GnomAD database, including 12,692 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 0.40 (12692 hom., cov: 32)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.172-224C>T		intron_variant	Intron 3 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.172-224C>T		intron_variant	Intron 3 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.172-224C>T		intron_variant	Intron 3 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61057 AN: 151946 Hom.: 12681 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.402 AC: 61104 AN: 152066 Hom.: 12692 Cov.: 32 AF XY: 0.409 AC XY: 30360 AN XY: 74318

African (AFR) AF: 0.341 AC: 14149 AN: 41490

American (AMR) AF: 0.498 AC: 7608 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1558 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2895 AN: 5156

South Asian (SAS) AF: 0.546 AC: 2629 AN: 4818

European-Finnish (FIN) AF: 0.420 AC: 4431 AN: 10560

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26543 AN: 67976

Other (OTH) AF: 0.402 AC: 849 AN: 2112

Alfa AF: 0.400 Hom.: 35868

Bravo AF: 0.401

Asia WGS AF: 0.535 AC: 1862 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	1.5
DANN	Benign	0.65
PhyloP100		-0.098
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10741150; hg19: chr10-128779958;