NM_001290223.2:c.3224+255C>T

Variant names:

• chr10-127344001-C-T
• rs943207
• NM_001290223.2:c.3224+255C>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.3224+255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,996 control chromosomes in the GnomAD database, including 20,783 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 0.51 (20783 hom., cov: 32)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.3224+255C>T		intron_variant	Intron 31 of 51	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.3224+255C>T		intron_variant	Intron 31 of 51	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.3161+255C>T		intron_variant	Intron 31 of 51	1		ENSP00000280333.6
DOCK1	ENST00000484400.5	n.378-198C>T		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77676 AN: 151874 Hom.: 20779 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.511 AC: 77709 AN: 151996 Hom.: 20783 Cov.: 32 AF XY: 0.505 AC XY: 37495 AN XY: 74310

African (AFR) AF: 0.390 AC: 16180 AN: 41444

American (AMR) AF: 0.476 AC: 7275 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2430 AN: 3464

East Asian (EAS) AF: 0.317 AC: 1637 AN: 5158

South Asian (SAS) AF: 0.576 AC: 2782 AN: 4830

European-Finnish (FIN) AF: 0.484 AC: 5100 AN: 10544

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40439 AN: 67952

Other (OTH) AF: 0.551 AC: 1161 AN: 2106

Alfa AF: 0.568 Hom.: 67003

Bravo AF: 0.503

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.67
PhyloP100		-0.49
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: rs943207; hg19: chr10-129142265; COSMIC: COSV54766397;