rs2296636

Positions:

• chr10-127362049-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.3284-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,594,248 control chromosomes in the GnomAD database, including 54,328 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 (4156 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50172 hom.)
• Consequence: DOCK1 NM_001290223.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK1	NM_001290223.2	c.3284-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000623213.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2	c.3284-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001290223.2
DOCK1	ENST00000280333.9	c.3221-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35188 AN: 151996 Hom.: 4148 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.232 AC: 53825 AN: 231856 Hom.: 6531 AF XY: 0.239 AC XY: 30058 AN XY: 125688

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.288

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.261 AC: 376501 AN: 1442134 Hom.: 50172 Cov.: 31 AF XY: 0.262 AC XY: 187389 AN XY: 716276

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.232 AC: 35215 AN: 152114 Hom.: 4156 Cov.: 33 AF XY: 0.232 AC XY: 17285 AN XY: 74348

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.238

Alfa AF: 0.246 Hom.: 5541

Bravo AF: 0.220

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.27

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: rs2296636; hg19: chr10-129160313; COSMIC: COSV54733782;