rs583608

chr2-224990155-G-Achr2-224990155-G-C

Variant summary

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

The NM_014689.3(DOCK10):c.123+52097C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,058 control chromosomes in the GnomAD database, including 22,721 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 0.52 (22721 hom., cov: 32)
• Consequence: DOCK10 NM_014689.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK10	NM_014689.3	c.123+52097C>T		intron_variant		ENST00000258390.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK10	ENST00000258390.12	c.123+52097C>T		intron_variant		5	NM_014689.3	P3

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78325 AN: 151940 Hom.: 22724 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.515 AC: 78350 AN: 152058 Hom.: 22721 Cov.: 32 AF XY: 0.526 AC XY: 39070 AN XY: 74340

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.512

Alfa AF: 0.558 Hom.: 3978

Bravo AF: 0.486

Asia WGS AF: 0.516 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	16
Dann	Benign	0.89

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: rs583608; hg19: chr2-225854872;