2-224775068-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_014689.3(DOCK10):c.5850C>T(p.Thr1950=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,614,024 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (96 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (96 hom.)
• Consequence: DOCK10 NM_014689.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00400

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 2-224775068-G-A is Benign according to our data. Variant chr2-224775068-G-A is described in ClinVar as [Benign]. Clinvar id is 783211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.004 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK10	NM_014689.3	c.5850C>T	p.Thr1950=	synonymous_variant	52/56	ENST00000258390.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK10	ENST00000258390.12	c.5850C>T	p.Thr1950=	synonymous_variant	52/56	5	NM_014689.3	P3

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2838 AN: 152214 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.00467 AC: 1163 AN: 249204 Hom.: 34 AF XY: 0.00356 AC XY: 481 AN XY: 135190

Gnomad AFR exome AF: 0.0654

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00199 AC: 2914 AN: 1461692 Hom.: 96 Cov.: 32 AF XY: 0.00174 AC XY: 1267 AN XY: 727128

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.00306

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.00437

GnomAD4 genome AF: 0.0187 AC: 2848 AN: 152332 Hom.: 96 Cov.: 32 AF XY: 0.0180 AC XY: 1339 AN XY: 74500

Gnomad4 AFR AF: 0.0648

Gnomad4 AMR AF: 0.00680

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00964 Hom.: 23

Bravo AF: 0.0214

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	7.4
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16866167; hg19: chr2-225639785;