19-11200160-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020812.4(DOCK6):c.6101+148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 601,554 control chromosomes in the GnomAD database, including 21,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (11456 hom., cov: 25)
  • Exomes 𝑓: 0.31 (9766 hom.)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

Genes affected

DOCK6 (HGNC:19189): (dedicator of cytokinesis 6) This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with small GTPases and are components of intracellular signaling networks. The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1. Mutations in this gene are associated with Adams-Oliver syndrome 2. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 19-11200160-C-A is Benign according to our data. Variant chr19-11200160-C-A is described in ClinVar as [Benign]. Clinvar id is 1281337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK6	NM_020812.4	c.6101+148G>T		intron_variant		ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK6	ENST00000294618.12	c.6101+148G>T		intron_variant		1	NM_020812.4	A2
DOCK6	ENST00000587656.6	c.6206+148G>T		intron_variant		5		P3
DOCK6	ENST00000587734.1	c.76-621G>T		intron_variant		5
DOCK6	ENST00000586702.1	n.1004+148G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 54858 AN: 127454 Hom.: 11449 Cov.: 25

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.307 AC: 145604 AN: 474074 Hom.: 9766 AF XY: 0.311 AC XY: 74030 AN XY: 238262

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.354

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.430 AC: 54876 AN: 127480 Hom.: 11456 Cov.: 25 AF XY: 0.430 AC XY: 26416 AN XY: 61414

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.413

Alfa AF: 0.0106 Hom.: 16

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

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.21
Dann	Benign	0.19

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: rs8101206; hg19: chr19-11310836; COSMIC: COSV53911749; COSMIC: COSV53911749;