NM_001290223.2:c.2445+7861A>G

Variant names:

• chr10-127069637-A-G
• rs9418832
• NM_001290223.2:c.2445+7861A>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+7861A>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 152,184 control chromosomes in the GnomAD database, including 64,666 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 (64666 hom., cov: 31)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.2445+7861A>G		intron_variant	Intron 23 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.2445+7861A>G		intron_variant	Intron 23 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.2382+7861A>G		intron_variant	Intron 23 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.922 AC: 140187 AN: 152066 Hom.: 64616 Cov.: 31

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: 0.945

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.922 AC: 140295 AN: 152184 Hom.: 64666 Cov.: 31 AF XY: 0.924 AC XY: 68703 AN XY: 74380

African (AFR) AF: 0.914 AC: 37958 AN: 41510

American (AMR) AF: 0.945 AC: 14446 AN: 15282

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

East Asian (EAS) AF: 0.923 AC: 4755 AN: 5152

South Asian (SAS) AF: 0.945 AC: 4547 AN: 4814

European-Finnish (FIN) AF: 0.930 AC: 9877 AN: 10616

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

European-Non Finnish (NFE) AF: 0.917 AC: 62355 AN: 68018

Other (OTH) AF: 0.930 AC: 1965 AN: 2114

Alfa AF: 0.924 Hom.: 10306

Bravo AF: 0.922

Asia WGS AF: 0.938 AC: 3264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.46
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: rs9418832; hg19: chr10-128867901;