rs17699030

chr19-11220266-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK6	NM_020812.4	c.3550+1585T>C		intron_variant		ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK6	ENST00000294618.12	c.3550+1585T>C		intron_variant		1	NM_020812.4	A2
DOCK6	ENST00000587656.6	c.3655+1585T>C		intron_variant		5		P3

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

Gnomad4 AFR AF: 0.00623

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0459

Gnomad4 NFE AF: 0.0406

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0410 Hom.: 62

Bravo AF: 0.0342

Asia WGS AF: 0.0660 AC: 233 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	3.3
Dann	Benign	0.50

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: rs17699030; hg19: chr19-11330942;