19-11223619-C-G

Position:

• chr19-11223619-C-G

Variant summary

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

The NM_020812.4(DOCK6):​c.2956-513G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,040 control chromosomes in the GnomAD database, including 3,136 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 0.18 (3136 hom., cov: 32)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.2956-513G>C		intron_variant		ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.2956-513G>C		intron_variant		1	NM_020812.4	ENSP00000294618	A2
DOCK6	ENST00000587656.6	c.3061-513G>C		intron_variant		5		ENSP00000468638	P3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27623 AN: 151922 Hom.: 3134 Cov.: 32

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.182 AC: 27669 AN: 152040 Hom.: 3136 Cov.: 32 AF XY: 0.184 AC XY: 13702 AN XY: 74332

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.157

Alfa AF: 0.158 Hom.: 280

Bravo AF: 0.198

Asia WGS AF: 0.185 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.38

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: rs4804155; hg19: chr19-11334295;