10-127381475-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105378551 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK1	NM_001290223.2	c.3807+107T>G		intron_variant		ENST00000623213.2
LOC105378551	XR_001747642.3	n.3760-2288A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK1	ENST00000623213.2	c.3807+107T>G		intron_variant		1	NM_001290223.2
DOCK1	ENST00000280333.9	c.3744+107T>G		intron_variant		1		P1

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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.278

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

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.277

Alfa AF: 0.142 Hom.: 239

Bravo AF: 0.268

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.1
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs1998864; hg19: chr10-129179739;