10-127070722-T-A

Variant names:

• chr10-127070722-T-A
• rs9418739
• NM_001290223.2:c.2445+8946T>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.2445+8946T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 150,530 control chromosomes in the GnomAD database, including 3,920 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 0.23 (3920 hom., cov: 29)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2445+8946T>A		intron_variant	Intron 23 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2445+8946T>A		intron_variant	Intron 23 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.2382+8946T>A		intron_variant	Intron 23 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.226 AC: 33965 AN: 150410 Hom.: 3917 Cov.: 29

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.226 AC: 33999 AN: 150530 Hom.: 3920 Cov.: 29 AF XY: 0.224 AC XY: 16408 AN XY: 73414

African (AFR) AF: 0.245 AC: 10036 AN: 40912

American (AMR) AF: 0.228 AC: 3399 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3458

East Asian (EAS) AF: 0.197 AC: 1009 AN: 5110

South Asian (SAS) AF: 0.343 AC: 1621 AN: 4720

European-Finnish (FIN) AF: 0.153 AC: 1592 AN: 10394

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14939 AN: 67710

Other (OTH) AF: 0.210 AC: 438 AN: 2088

Alfa AF: 0.115 Hom.: 182

Bravo AF: 0.228

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.24
DANN	Benign	0.78
PhyloP100		-1.6
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: rs9418739; hg19: chr10-128868986;