chr10-127362049-C-T

Variant names:

• chr10-127362049-C-T
• rs2296636
• NM_001290223.2:c.3284-15C>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.3284-15C>T variant causes a 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• Publications: 7 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]

ENSG00000298283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.3284-15C>T		intron_variant	Intron 32 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.3284-15C>T		intron_variant	Intron 32 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.3221-15C>T		intron_variant	Intron 32 of 51	1		ENSP00000280333.6
ENSG00000298283	ENST00000754441.1	n.722G>A		non_coding_transcript_exon_variant	Exon 5 of 5

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

GnomAD2 exomes AF: 0.232 AC: 53825 AN: 231856 AF XY: 0.239

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 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

African (AFR) AF: 0.183 AC: 5945 AN: 32442

American (AMR) AF: 0.115 AC: 4693 AN: 40972

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5199 AN: 25432

East Asian (EAS) AF: 0.281 AC: 11094 AN: 39440

South Asian (SAS) AF: 0.283 AC: 23422 AN: 82750

European-Finnish (FIN) AF: 0.244 AC: 12935 AN: 53010

Middle Eastern (MID) AF: 0.201 AC: 1140 AN: 5658

European-Non Finnish (NFE) AF: 0.269 AC: 297154 AN: 1102908

Other (OTH) AF: 0.251 AC: 14919 AN: 59522

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

African (AFR) AF: 0.194 AC: 8050 AN: 41502

American (AMR) AF: 0.174 AC: 2661 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1309 AN: 5168

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4826

European-Finnish (FIN) AF: 0.240 AC: 2530 AN: 10556

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17915 AN: 67992

Other (OTH) AF: 0.238 AC: 502 AN: 2106

Alfa AF: 0.246 Hom.: 7800

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
PhyloP100		0.97
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: rs2296636; hg19: chr10-129160313; COSMIC: COSV54733782;