10-127381475-T-G

Variant names:

• chr10-127381475-T-G
• rs1998864
• NM_001290223.2:c.3807+107T>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.3807+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 911,482 control chromosomes in the GnomAD database, including 34,256 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 0.26 (5504 hom., cov: 33)
  • Exomes 𝑓: 0.27 (28752 hom.)
• Consequence: DOCK1 NM_001290223.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342
• Publications: 0 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]

ENSG00000298283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 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.3807+107T>G		intron	N/A	NP_001277152.2
	DOCK1	NM_001377543.1		c.3744+107T>G		intron	N/A	NP_001364472.1
	DOCK1	NM_001377544.1		c.3780+107T>G		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.3807+107T>G		intron	N/A	ENSP00000485033.1
	DOCK1	ENST00000280333.9	TSL:1	c.3744+107T>G		intron	N/A	ENSP00000280333.6
	ENSG00000298283	ENST00000754441.1		n.201-2288A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39563 AN: 152070 Hom.: 5499 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.267 AC: 202620 AN: 759294 Hom.: 28752 AF XY: 0.268 AC XY: 102513 AN XY: 382676

African (AFR) AF: 0.200 AC: 3537 AN: 17646

American (AMR) AF: 0.476 AC: 8941 AN: 18788

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 5046 AN: 15940

East Asian (EAS) AF: 0.451 AC: 14342 AN: 31824

South Asian (SAS) AF: 0.297 AC: 11306 AN: 38102

European-Finnish (FIN) AF: 0.266 AC: 10140 AN: 38188

Middle Eastern (MID) AF: 0.369 AC: 1398 AN: 3790

European-Non Finnish (NFE) AF: 0.247 AC: 138221 AN: 560186

Other (OTH) AF: 0.278 AC: 9689 AN: 34830

GnomAD4 genome AF: 0.260 AC: 39599 AN: 152188 Hom.: 5504 Cov.: 33 AF XY: 0.265 AC XY: 19733 AN XY: 74412

African (AFR) AF: 0.198 AC: 8223 AN: 41524

American (AMR) AF: 0.380 AC: 5807 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2250 AN: 5172

South Asian (SAS) AF: 0.301 AC: 1450 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2622 AN: 10596

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17209 AN: 67998

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.145 Hom.: 250

Bravo AF: 0.268

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.1
DANN	Benign	0.83
PhyloP100		-0.34
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: rs1998864; hg19: chr10-129179739;