rs9733352

Variant names:

• chr10-126979126-G-C
• rs9733352
• NM_001290223.2:c.171+1138G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-126979126-G-C
• chr10-126979126-G-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.171+1138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,024 control chromosomes in the GnomAD database, including 13,052 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 0.41 (13052 hom., cov: 32)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.171+1138G>C		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.171+1138G>C		intron_variant	Intron 3 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.171+1138G>C		intron_variant	Intron 3 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61757 AN: 151906 Hom.: 13042 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.407 AC: 61802 AN: 152024 Hom.: 13052 Cov.: 32 AF XY: 0.414 AC XY: 30773 AN XY: 74288

African (AFR) AF: 0.341 AC: 14147 AN: 41462

American (AMR) AF: 0.498 AC: 7613 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.639 AC: 3301 AN: 5168

South Asian (SAS) AF: 0.549 AC: 2643 AN: 4814

European-Finnish (FIN) AF: 0.435 AC: 4589 AN: 10550

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

European-Non Finnish (NFE) AF: 0.392 AC: 26641 AN: 67968

Other (OTH) AF: 0.408 AC: 861 AN: 2112

Alfa AF: 0.278 Hom.: 741

Bravo AF: 0.405

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.51
PhyloP100		1.3
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: rs9733352; hg19: chr10-128777390;