rs737337

Positions:

• chr19-11236817-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020812.4(DOCK6):​c.2136A>G​(p.Thr712=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,553,570 control chromosomes in the GnomAD database, including 15,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4814 hom., cov: 32)
  • Exomes 𝑓: 0.10 (10987 hom.)
• Consequence: DOCK6 NM_020812.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.24

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-11236817-T-C is Benign according to our data. Variant chr19-11236817-T-C is described in ClinVar as [Benign]. Clinvar id is 1170730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11236817-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK6	NM_020812.4	c.2136A>G	p.Thr712=	synonymous_variant	19/48	ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK6	ENST00000294618.12	c.2136A>G	p.Thr712=	synonymous_variant	19/48	1	NM_020812.4	A2
DOCK6	ENST00000587656.6	c.2136A>G	p.Thr712=	synonymous_variant	19/49	5		P3
DOCK6	ENST00000590680.5	c.480A>G	p.Thr160=	synonymous_variant	5/11	5
DOCK6	ENST00000591750.1	n.2105A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30275 AN: 151990 Hom.: 4799 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0830

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.151 AC: 23987 AN: 158802 Hom.: 2824 AF XY: 0.141 AC XY: 11908 AN XY: 84448

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.262

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.0894

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.101 AC: 142035 AN: 1401462 Hom.: 10987 Cov.: 32 AF XY: 0.102 AC XY: 70294 AN XY: 691542

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.0278

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0900

Gnomad4 NFE exome AF: 0.0782

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.199 AC: 30342 AN: 152108 Hom.: 4814 Cov.: 32 AF XY: 0.201 AC XY: 14942 AN XY: 74378

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0847

Gnomad4 NFE AF: 0.0830

Gnomad4 OTH AF: 0.170

Alfa AF: 0.104 Hom.: 3370

Bravo AF: 0.223

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 16, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.42

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: rs737337; hg19: chr19-11347493; COSMIC: COSV52948838; COSMIC: COSV52948838;