rs12772251

Variant names:

• chr10-127298741-A-G
• rs12772251
• NM_001290223.2:c.3045-40265A>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.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
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	NM_001290223.2	MANE Select	c.3045-40265A>G		intron	N/A	NP_001277152.2	A0A096LNH6
	DOCK1	NM_001377543.1		c.2982-40265A>G		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.3018-40265A>G		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.3045-40265A>G		intron	N/A	ENSP00000485033.1	A0A096LNH6
	DOCK1	ENST00000280333.9	TSL:1	c.2982-40265A>G		intron	N/A	ENSP00000280333.6	Q14185
	DOCK1	ENST00000939683.1		c.3045-40265A>G		intron	N/A	ENSP00000609742.1

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

African (AFR) AF: 0.240 AC: 9950 AN: 41518

American (AMR) AF: 0.127 AC: 1937 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3468

East Asian (EAS) AF: 0.228 AC: 1176 AN: 5158

South Asian (SAS) AF: 0.113 AC: 545 AN: 4816

European-Finnish (FIN) AF: 0.146 AC: 1544 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7456 AN: 68018

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.118 Hom.: 603

Bravo AF: 0.157

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.37
PhyloP100		-1.4
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: rs12772251; hg19: chr10-129097005;