10-127066410-T-C

Variant names:

• chr10-127066410-T-C
• rs7917277
• NM_001290223.2:c.2445+4634T>C

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+4634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,236 control chromosomes in the GnomAD database, including 64,837 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 (64837 hom., cov: 32)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.933 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.2445+4634T>C		intron	N/A	NP_001277152.2	A0A096LNH6
	DOCK1	NM_001377543.1		c.2382+4634T>C		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.2418+4634T>C		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.2445+4634T>C		intron	N/A	ENSP00000485033.1	A0A096LNH6
	DOCK1	ENST00000280333.9	TSL:1	c.2382+4634T>C		intron	N/A	ENSP00000280333.6	Q14185
	DOCK1	ENST00000939683.1		c.2445+4634T>C		intron	N/A	ENSP00000609742.1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140390 AN: 152118 Hom.: 64788 Cov.: 32

Gnomad AFR AF: 0.919

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: 0.916

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.923 AC: 140499 AN: 152236 Hom.: 64837 Cov.: 32 AF XY: 0.925 AC XY: 68820 AN XY: 74430

African (AFR) AF: 0.919 AC: 38147 AN: 41526

American (AMR) AF: 0.945 AC: 14468 AN: 15302

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

East Asian (EAS) AF: 0.922 AC: 4758 AN: 5158

South Asian (SAS) AF: 0.944 AC: 4550 AN: 4822

European-Finnish (FIN) AF: 0.931 AC: 9871 AN: 10608

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

European-Non Finnish (NFE) AF: 0.916 AC: 62351 AN: 68034

Other (OTH) AF: 0.931 AC: 1962 AN: 2108

Alfa AF: 0.926 Hom.: 11361

Bravo AF: 0.924

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.36
PhyloP100		-1.9
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: rs7917277; hg19: chr10-128864674;