10-127007143-T-C

Variant names:

• chr10-127007143-T-C
• rs9418677
• NM_001290223.2:c.986-1589T>C

Variant summary

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

The NM_001290223.2(DOCK1):​c.986-1589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,876 control chromosomes in the GnomAD database, including 14,243 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 0.43 (14243 hom., cov: 31)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 5 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]

ENSG00000223528 (HGNC:58348):

LOC107984059 (HGNC:):

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 = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.986-1589T>C		intron_variant	Intron 10 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.986-1589T>C		intron_variant	Intron 10 of 51	1	NM_001290223.2	ENSP00000485033.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65649 AN: 151758 Hom.: 14237 Cov.: 31

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.433 AC: 65698 AN: 151876 Hom.: 14243 Cov.: 31 AF XY: 0.435 AC XY: 32254 AN XY: 74180

African (AFR) AF: 0.447 AC: 18524 AN: 41424

American (AMR) AF: 0.425 AC: 6494 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1323 AN: 3462

East Asian (EAS) AF: 0.522 AC: 2664 AN: 5104

South Asian (SAS) AF: 0.346 AC: 1664 AN: 4808

European-Finnish (FIN) AF: 0.493 AC: 5193 AN: 10532

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28482 AN: 67956

Other (OTH) AF: 0.444 AC: 936 AN: 2110

Alfa AF: 0.420 Hom.: 26538

Bravo AF: 0.434

Asia WGS AF: 0.452 AC: 1571 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	2.4
DANN	Benign	0.84
PhyloP100		-0.26
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: rs9418677; hg19: chr10-128805407;