19-11232027-A-G

Variant names:

• chr19-11232027-A-G
• rs12979813
• NM_020812.4:c.2718+1176T>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.2718+1176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,056 control chromosomes in the GnomAD database, including 7,970 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 0.29 (7970 hom., cov: 32)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 14 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: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.2718+1176T>C		intron_variant	Intron 22 of 47	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.2718+1176T>C		intron_variant	Intron 22 of 47	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587656.6	c.2823+158T>C		intron_variant	Intron 23 of 48	5		ENSP00000468638.2
DOCK6	ENST00000590680.5	c.1059+1176T>C		intron_variant	Intron 8 of 10	5		ENSP00000467191.1
DOCK6	ENST00000585904.1	c.426+158T>C		intron_variant	Intron 3 of 4	4		ENSP00000465767.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44133 AN: 151938 Hom.: 7954 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.291 AC: 44207 AN: 152056 Hom.: 7970 Cov.: 32 AF XY: 0.291 AC XY: 21614 AN XY: 74338

African (AFR) AF: 0.517 AC: 21414 AN: 41438

American (AMR) AF: 0.277 AC: 4225 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3470

East Asian (EAS) AF: 0.326 AC: 1685 AN: 5174

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4818

European-Finnish (FIN) AF: 0.191 AC: 2026 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12580 AN: 67978

Other (OTH) AF: 0.254 AC: 538 AN: 2116

Alfa AF: 0.233 Hom.: 8481

Bravo AF: 0.310

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.91
PhyloP100		-0.089
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		1.9
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: rs12979813; hg19: chr19-11342703; COSMIC: COSV53923153; COSMIC: COSV53923153;