chr10-127451811-A-G

Variant names:

• chr10-127451811-A-G
• rs3740543
• NM_001290223.2:c.*384A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.*384A>G		3_prime_UTR_variant	Exon 52 of 52	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.*384A>G		3_prime_UTR_variant	Exon 52 of 52	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.*384A>G		3_prime_UTR_variant	Exon 52 of 52	1		ENSP00000280333.6

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

African (AFR) AF: 0.189 AC: 681 AN: 3594

American (AMR) AF: 0.469 AC: 1656 AN: 3532

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1481 AN: 3108

East Asian (EAS) AF: 0.279 AC: 940 AN: 3372

South Asian (SAS) AF: 0.482 AC: 9581 AN: 19884

European-Finnish (FIN) AF: 0.411 AC: 2810 AN: 6834

Middle Eastern (MID) AF: 0.492 AC: 247 AN: 502

European-Non Finnish (NFE) AF: 0.497 AC: 35714 AN: 71816

Other (OTH) AF: 0.481 AC: 3104 AN: 6452

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

African (AFR) AF: 0.261 AC: 10832 AN: 41440

American (AMR) AF: 0.544 AC: 8302 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3472

East Asian (EAS) AF: 0.387 AC: 1993 AN: 5152

South Asian (SAS) AF: 0.524 AC: 2516 AN: 4806

European-Finnish (FIN) AF: 0.447 AC: 4711 AN: 10546

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36581 AN: 67950

Other (OTH) AF: 0.470 AC: 990 AN: 2108

Alfa AF: 0.517 Hom.: 38189

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
PhyloP100		-0.43
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: rs3740543; hg19: chr10-129250075;