rs3740543

Positions:

• chr10-127451811-A-G
• chr10-127451811-A-T

Variant summary

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

The NM_001290223.2(DOCK1):​c.*384A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 271,048 control chromosomes in the GnomAD database, including 30,222 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 (16530 hom., cov: 32)
  • Exomes 𝑓: 0.47 (13692 hom.)
• Consequence: DOCK1 NM_001290223.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.*384A>G		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.*384A>G		3_prime_UTR_variant	52/52	1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.*384A>G		3_prime_UTR_variant	52/52	1		ENSP00000280333	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68288 AN: 151836 Hom.: 16518 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.472 AC: 56214 AN: 119094 Hom.: 13692 Cov.: 2 AF XY: 0.471 AC XY: 29550 AN XY: 62756

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.450 AC: 68333 AN: 151954 Hom.: 16530 Cov.: 32 AF XY: 0.448 AC XY: 33254 AN XY: 74272

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.470

Alfa AF: 0.529 Hom.: 28320

Bravo AF: 0.444

Asia WGS AF: 0.457 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.76

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: rs3740543; hg19: chr10-129250075;