rs4635002

Positions:

• chr10-127064415-A-C
• chr10-127064415-A-G
• chr10-127064415-A-T

Variant summary

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

The ENST00000623213.2(DOCK1):​c.2445+2639A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,242 control chromosomes in the GnomAD database, including 65,092 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 0.92 (65092 hom., cov: 34)
• Consequence: DOCK1 ENST00000623213.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2445+2639A>C		intron_variant		ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2445+2639A>C		intron_variant		1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.2382+2639A>C		intron_variant		1		ENSP00000280333	P1

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140674 AN: 152124 Hom.: 65043 Cov.: 34

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.925 AC: 140783 AN: 152242 Hom.: 65092 Cov.: 34 AF XY: 0.927 AC XY: 68952 AN XY: 74420

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.947

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.932

Alfa AF: 0.923 Hom.: 47377

Bravo AF: 0.926

Asia WGS AF: 0.942 AC: 3276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.35

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: rs4635002; hg19: chr10-128862679;