rs2050305

Variant names:

• chr10-127221414-C-T
• rs2050305
• NM_001290223.2:c.2848-26594C>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.2848-26594C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,922 control chromosomes in the GnomAD database, including 9,812 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 0.35 (9812 hom., cov: 32)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2848-26594C>T		intron_variant	Intron 27 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2848-26594C>T		intron_variant	Intron 27 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.2785-26594C>T		intron_variant	Intron 27 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53616 AN: 151804 Hom.: 9808 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.353 AC: 53639 AN: 151922 Hom.: 9812 Cov.: 32 AF XY: 0.354 AC XY: 26263 AN XY: 74238

African (AFR) AF: 0.263 AC: 10910 AN: 41430

American (AMR) AF: 0.410 AC: 6256 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1123 AN: 3464

East Asian (EAS) AF: 0.422 AC: 2165 AN: 5132

South Asian (SAS) AF: 0.383 AC: 1837 AN: 4802

European-Finnish (FIN) AF: 0.392 AC: 4141 AN: 10558

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26076 AN: 67960

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.377 Hom.: 18404

Bravo AF: 0.351

Asia WGS AF: 0.377 AC: 1308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.42
PhyloP100		1.3
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: rs2050305; hg19: chr10-129019678;