chr2-224891779-C-G

Variant names:

• chr2-224891779-C-G
• rs9288593
• NM_014689.3:c.416+4516G>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.416+4516G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,678 control chromosomes in the GnomAD database, including 14,932 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 0.40 (14932 hom., cov: 32)
• Consequence: DOCK10 NM_014689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 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.416+4516G>C		intron	N/A	NP_055504.2	Q96BY6-1
	DOCK10	NM_001363762.1		c.455+4516G>C		intron	N/A	NP_001350691.1	A0A2R8YD85
	DOCK10	NM_001290263.2		c.398+4516G>C		intron	N/A	NP_001277192.1	Q96BY6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK10	ENST00000258390.12	TSL:5 MANE Select	c.416+4516G>C		intron	N/A	ENSP00000258390.7	Q96BY6-1
	DOCK10	ENST00000409592.7	TSL:1	c.398+4516G>C		intron	N/A	ENSP00000386694.3	Q96BY6-3
	DOCK10	ENST00000492369.5	TSL:1	n.484+4516G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60780 AN: 151560 Hom.: 14909 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.401 AC: 60855 AN: 151678 Hom.: 14932 Cov.: 32 AF XY: 0.391 AC XY: 29021 AN XY: 74186

African (AFR) AF: 0.692 AC: 28665 AN: 41432

American (AMR) AF: 0.239 AC: 3652 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3468

East Asian (EAS) AF: 0.0639 AC: 331 AN: 5180

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4824

European-Finnish (FIN) AF: 0.316 AC: 3329 AN: 10536

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

European-Non Finnish (NFE) AF: 0.319 AC: 21602 AN: 67648

Other (OTH) AF: 0.346 AC: 729 AN: 2108

Alfa AF: 0.122 Hom.: 156

Bravo AF: 0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.50
DANN	Benign	0.34
PhyloP100		-1.1
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: rs9288593; hg19: chr2-225756496;