rs4804155

Variant names:

• chr19-11223619-C-G
• rs4804155
• NM_020812.4:c.2956-513G>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.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
• Publications: 15 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 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Adams-Oliver syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

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 (AFR) allele frequency at 95% confidence interval = 0.304 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK6	NM_020812.4	MANE Select	c.2956-513G>C		intron	N/A	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.3061-513G>C		intron	N/A	NP_001354759.1	K7ESB7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK6	ENST00000294618.12	TSL:1 MANE Select	c.2956-513G>C		intron	N/A	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587656.6	TSL:5	c.3061-513G>C		intron	N/A	ENSP00000468638.2	K7ESB7

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

African (AFR) AF: 0.308 AC: 12785 AN: 41446

American (AMR) AF: 0.222 AC: 3389 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5164

South Asian (SAS) AF: 0.155 AC: 748 AN: 4812

European-Finnish (FIN) AF: 0.123 AC: 1296 AN: 10578

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7542 AN: 68000

Other (OTH) AF: 0.157 AC: 331 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.38
PhyloP100		-1.5
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: rs4804155; hg19: chr19-11334295;