NM_001290223.2:c.3044+14892G>A

Variant names:

• chr10-127272321-G-A
• rs2498947
• NM_001290223.2:c.3044+14892G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290223.2(DOCK1):​c.3044+14892G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,100 control chromosomes in the GnomAD database, including 7,110 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 0.27 (7109 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	NM_001290223.2	MANE Select	c.3044+14892G>A		intron	N/A	NP_001277152.2
	DOCK1	NM_001377543.1		c.2981+14892G>A		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.3017+14892G>A		intron	N/A	NP_001364473.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	ENST00000623213.2	TSL:1 MANE Select	c.3044+14892G>A		intron	N/A	ENSP00000485033.1
	DOCK1	ENST00000280333.9	TSL:1	c.2981+14892G>A		intron	N/A	ENSP00000280333.6
	DOCK1	ENST00000484400.5	TSL:3	n.197+14892G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41621 AN: 151980 Hom.: 7112 Cov.: 33

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.274 AC: 41618 AN: 152098 Hom.: 7109 Cov.: 33 AF XY: 0.277 AC XY: 20592 AN XY: 74346

African (AFR) AF: 0.0694 AC: 2882 AN: 41522

American (AMR) AF: 0.337 AC: 5140 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3466

East Asian (EAS) AF: 0.232 AC: 1198 AN: 5164

South Asian (SAS) AF: 0.518 AC: 2495 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3116 AN: 10582

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24195 AN: 67956

Other (OTH) AF: 0.307 AC: 649 AN: 2112

Alfa AF: 0.330 Hom.: 4949

Bravo AF: 0.267

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		1.3
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: rs2498947; hg19: chr10-129070585;