10-127007143-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

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 = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK1	NM_001290223.2	c.986-1589T>C		intron_variant		ENST00000623213.2
LOC107984059	XR_001747639.2	n.75+268A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2	c.986-1589T>C		intron_variant		1	NM_001290223.2
	ENST00000601242.5	n.152-5534A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.444

Alfa AF: 0.414 Hom.: 17904

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9418677; hg19: chr10-128805407;