rs1051039

Positions:

• chr10-127452339-G-C
• chr10-127452339-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290223.2(DOCK1):​c.*912G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,168 control chromosomes in the GnomAD database, including 16,455 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 0.45 (16415 hom., cov: 31)
  • Exomes 𝑓: 0.45 (40 hom.)
• Consequence: DOCK1 NM_001290223.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.*912G>C		3_prime_UTR_variant	52/52	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.*912G>C		3_prime_UTR_variant	52/52	1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.*912G>C		3_prime_UTR_variant	52/52	1		ENSP00000280333	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 67770 AN: 150618 Hom.: 16403 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.454 AC: 197 AN: 434 Hom.: 40 Cov.: 0 AF XY: 0.469 AC XY: 123 AN XY: 262

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.450 AC: 67813 AN: 150734 Hom.: 16415 Cov.: 31 AF XY: 0.448 AC XY: 32928 AN XY: 73514

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.472

Alfa AF: 0.474 Hom.: 2172

Bravo AF: 0.441

Asia WGS AF: 0.451 AC: 1564 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.64

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: rs1051039; hg19: chr10-129250603; COSMIC: COSV54741652; COSMIC: COSV54741652;