rs17699030

Variant names:

• chr19-11220266-A-G
• rs17699030
• NM_020812.4:c.3550+1585T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020812.4(DOCK6):​c.3550+1585T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 152,190 control chromosomes in the GnomAD database, including 141 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 0.036 (141 hom., cov: 32)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 10 publications found

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]

DOCK6-AS1 (HGNC:56684): (DOCK6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK6	NM_020812.4	MANE Select	c.3550+1585T>C		intron	N/A	NP_065863.2
	DOCK6-AS1	NR_186345.1		n.826A>G		non_coding_transcript_exon	Exon 3 of 3
	DOCK6	NM_001367830.1		c.3655+1585T>C		intron	N/A	NP_001354759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK6	ENST00000294618.12	TSL:1 MANE Select	c.3550+1585T>C		intron	N/A	ENSP00000294618.6
	DOCK6-AS1	ENST00000588634.2	TSL:4	n.919A>G		non_coding_transcript_exon	Exon 4 of 4
	DOCK6	ENST00000587656.6	TSL:5	c.3655+1585T>C		intron	N/A	ENSP00000468638.2

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5422 AN: 152072 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.00625

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.0459

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0387

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

GnomAD4 genome AF: 0.0357 AC: 5426 AN: 152190 Hom.: 141 Cov.: 32 AF XY: 0.0383 AC XY: 2851 AN XY: 74394

African (AFR) AF: 0.00623 AC: 259 AN: 41542

American (AMR) AF: 0.0408 AC: 623 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.114 AC: 591 AN: 5176

South Asian (SAS) AF: 0.100 AC: 482 AN: 4820

European-Finnish (FIN) AF: 0.0459 AC: 486 AN: 10594

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0406 AC: 2763 AN: 67998

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0396 Hom.: 289

Bravo AF: 0.0342

Asia WGS AF: 0.0660 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.50
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17699030; hg19: chr19-11330942;