rs4635002

Variant names:

• chr10-127064415-A-C
• rs4635002
• NM_001290223.2:c.2445+2639A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377543.1(DOCK1):​c.2382+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 NM_001377543.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377543.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	NM_001290223.2	MANE Select	c.2445+2639A>C		intron	N/A	NP_001277152.2
	DOCK1	NM_001377543.1		c.2382+2639A>C		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.2418+2639A>C		intron	N/A	NP_001364473.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	ENST00000623213.2	TSL:1 MANE Select	c.2445+2639A>C		intron	N/A	ENSP00000485033.1
	DOCK1	ENST00000280333.9	TSL:1	c.2382+2639A>C		intron	N/A	ENSP00000280333.6
	DOCK1	ENST00000939683.1		c.2445+2639A>C		intron	N/A	ENSP00000609742.1

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

African (AFR) AF: 0.924 AC: 38371 AN: 41544

American (AMR) AF: 0.947 AC: 14483 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.959 AC: 3328 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4771 AN: 5170

South Asian (SAS) AF: 0.947 AC: 4568 AN: 4824

European-Finnish (FIN) AF: 0.931 AC: 9866 AN: 10598

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62359 AN: 68012

Other (OTH) AF: 0.932 AC: 1973 AN: 2116

Alfa AF: 0.923 Hom.: 66567

Bravo AF: 0.926

Asia WGS AF: 0.942 AC: 3276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.35
PhyloP100		-0.28
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: rs4635002; hg19: chr10-128862679;