10-127272321-G-A

Position:

• chr10-127272321-G-A

Variant summary

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

The NM_001290223.2(DOCK1):​c.3044+14892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,100 control chromosomes in the GnomAD database, including 7,110 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 0.27 (7109 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.3044+14892G>A		intron_variant		ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.3044+14892G>A		intron_variant		1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.2981+14892G>A		intron_variant		1		ENSP00000280333	P1
DOCK1	ENST00000484400.5	n.197+14892G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41621 AN: 151980 Hom.: 7112 Cov.: 33

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.274 AC: 41618 AN: 152098 Hom.: 7109 Cov.: 33 AF XY: 0.277 AC XY: 20592 AN XY: 74346

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.307

Alfa AF: 0.329 Hom.: 4442

Bravo AF: 0.267

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.71

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: rs2498947; hg19: chr10-129070585;