2-224953847-A-G

Position:

• chr2-224953847-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014689.3(DOCK10):​c.124-22179T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,134 control chromosomes in the GnomAD database, including 5,015 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 0.24 (5015 hom., cov: 32)
• Consequence: DOCK10 NM_014689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844

Genes affected

DOCK10 (HGNC:23479): (dedicator of cytokinesis 10) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family are guanosine nucleotide exchange factors for Rho GTPases and defined by the presence of conserved DOCK-homology regions. The encoded protein belongs to the D (or Zizimin) subfamily of DOCK proteins, which also contain an N-terminal pleckstrin homology domain. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK10	NM_014689.3	c.124-22179T>C		intron_variant		ENST00000258390.12	NP_055504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK10	ENST00000258390.12	c.124-22179T>C		intron_variant		5	NM_014689.3	ENSP00000258390	P3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36979 AN: 152016 Hom.: 5006 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.243 AC: 37020 AN: 152134 Hom.: 5015 Cov.: 32 AF XY: 0.247 AC XY: 18359 AN XY: 74358

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.273

Alfa AF: 0.278 Hom.: 8076

Bravo AF: 0.230

Asia WGS AF: 0.331 AC: 1150 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	4.7
DANN	Benign	0.50

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: rs11686538; hg19: chr2-225818564;