chr10-127069586-A-G

Variant names:

• chr10-127069586-A-G
• rs9418737
• NM_001290223.2:c.2445+7810A>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.2445+7810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 152,264 control chromosomes in the GnomAD database, including 64,693 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 (64693 hom., cov: 32)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290223.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	NM_001290223.2	MANE Select	c.2445+7810A>G		intron	N/A	NP_001277152.2
	DOCK1	NM_001377543.1		c.2382+7810A>G		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.2418+7810A>G		intron	N/A	NP_001364473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	ENST00000623213.2	TSL:1 MANE Select	c.2445+7810A>G		intron	N/A	ENSP00000485033.1
	DOCK1	ENST00000280333.9	TSL:1	c.2382+7810A>G		intron	N/A	ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140252 AN: 152146 Hom.: 64643 Cov.: 32

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.922 AC: 140360 AN: 152264 Hom.: 64693 Cov.: 32 AF XY: 0.924 AC XY: 68756 AN XY: 74442

African (AFR) AF: 0.914 AC: 37986 AN: 41544

American (AMR) AF: 0.945 AC: 14456 AN: 15294

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

East Asian (EAS) AF: 0.923 AC: 4772 AN: 5172

South Asian (SAS) AF: 0.944 AC: 4550 AN: 4820

European-Finnish (FIN) AF: 0.931 AC: 9872 AN: 10606

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

European-Non Finnish (NFE) AF: 0.917 AC: 62367 AN: 68038

Other (OTH) AF: 0.930 AC: 1965 AN: 2112

Alfa AF: 0.923 Hom.: 10304

Bravo AF: 0.922

Asia WGS AF: 0.938 AC: 3264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.19
PhyloP100		-0.98
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: rs9418737; hg19: chr10-128867850;