rs12772251

Positions:

• chr10-127298741-A-G

Variant summary

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

The NM_001290223.2(DOCK1):​c.3045-40265A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,174 control chromosomes in the GnomAD database, including 2,108 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 0.15 (2108 hom., cov: 33)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.3045-40265A>G		intron_variant		ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.3045-40265A>G		intron_variant		1	NM_001290223.2	ENSP00000485033
DOCK1	ENST00000280333.9	c.2982-40265A>G		intron_variant		1		ENSP00000280333	P1
DOCK1	ENST00000484400.5	n.198-40265A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23349 AN: 152056 Hom.: 2107 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.154 AC: 23371 AN: 152174 Hom.: 2108 Cov.: 33 AF XY: 0.155 AC XY: 11533 AN XY: 74388

Gnomad4 AFR AF: 0.240

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.139

Alfa AF: 0.118 Hom.: 549

Bravo AF: 0.157

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.37

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: rs12772251; hg19: chr10-129097005;