NM_014689.3:c.124-22179T>C

Variant names:

• chr2-224953847-A-G
• rs11686538
• NM_014689.3:c.124-22179T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014689.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK10	NM_014689.3	MANE Select	c.124-22179T>C		intron	N/A	NP_055504.2	Q96BY6-1
	DOCK10	NM_001363762.1		c.163-22179T>C		intron	N/A	NP_001350691.1	A0A2R8YD85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK10	ENST00000258390.12	TSL:5 MANE Select	c.124-22179T>C		intron	N/A	ENSP00000258390.7	Q96BY6-1
	DOCK10	ENST00000492369.5	TSL:1	n.192-22179T>C		intron	N/A
	DOCK10	ENST00000645028.1		c.163-22179T>C		intron	N/A	ENSP00000493664.1	A0A2R8YD85

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

African (AFR) AF: 0.127 AC: 5261 AN: 41524

American (AMR) AF: 0.244 AC: 3727 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3466

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5166

South Asian (SAS) AF: 0.331 AC: 1598 AN: 4822

European-Finnish (FIN) AF: 0.327 AC: 3450 AN: 10566

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19272 AN: 67984

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.274 Hom.: 9991

Bravo AF: 0.230

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.50
PhyloP100		0.84
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: rs11686538; hg19: chr2-225818564;