rs10741150

chr10-126981694-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	UniProt
DOCK1	NM_001290223.2	c.172-224C>T		intron_variant		ENST00000623213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2	c.172-224C>T		intron_variant		1	NM_001290223.2
DOCK1	ENST00000280333.9	c.172-224C>T		intron_variant		1		P1

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

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.402

Alfa AF: 0.402 Hom.: 25595

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10741150; hg19: chr10-128779958;