rs7068699

Variant names:

• chr10-127443758-C-G
• rs7068699
• NM_001290223.2:c.5260-368C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-127443758-C-G
• chr10-127443758-C-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.5260-368C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,896 control chromosomes in the GnomAD database, including 12,685 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 0.40 (12685 hom., cov: 31)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 2 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.5260-368C>G		intron_variant	Intron 49 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.5260-368C>G		intron_variant	Intron 49 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.5197-368C>G		intron_variant	Intron 49 of 51	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61230 AN: 151778 Hom.: 12667 Cov.: 31

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.403 AC: 61284 AN: 151896 Hom.: 12685 Cov.: 31 AF XY: 0.400 AC XY: 29700 AN XY: 74234

African (AFR) AF: 0.323 AC: 13405 AN: 41444

American (AMR) AF: 0.369 AC: 5634 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1191 AN: 3466

East Asian (EAS) AF: 0.601 AC: 3092 AN: 5146

South Asian (SAS) AF: 0.424 AC: 2037 AN: 4808

European-Finnish (FIN) AF: 0.366 AC: 3863 AN: 10546

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30780 AN: 67910

Other (OTH) AF: 0.411 AC: 863 AN: 2100

Alfa AF: 0.299 Hom.: 799

Bravo AF: 0.400

Asia WGS AF: 0.498 AC: 1730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.40
PhyloP100		-1.6
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: rs7068699; hg19: chr10-129242022;