19-11202580-G-A

Variant names:

• chr19-11202580-G-A
• rs3745682
• NM_020812.4:c.5361+4C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020812.4(DOCK6):​c.5361+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,742 control chromosomes in the GnomAD database, including 132,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10249 hom., cov: 32)
  • Exomes 𝑓: 0.41 (121875 hom.)
• Consequence: DOCK6 NM_020812.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.20
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 19-11202580-G-A is Benign according to our data. Variant chr19-11202580-G-A is described in ClinVar as Benign. ClinVar VariationId is 261358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 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.5361+4C>T		splice_region intron	N/A	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.5466+4C>T		splice_region 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.5361+4C>T		splice_region intron	N/A	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587656.6	TSL:5	c.5466+4C>T		splice_region intron	N/A	ENSP00000468638.2	K7ESB7
	DOCK6	ENST00000588666.1	TSL:5	c.309+4C>T		splice_region intron	N/A	ENSP00000467231.1	K7EP51

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54543 AN: 151988 Hom.: 10249 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.359

GnomAD2 exomes AF: 0.394 AC: 98152 AN: 248936 AF XY: 0.401

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.461

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.406 AC: 594037 AN: 1461636 Hom.: 121875 Cov.: 76 AF XY: 0.409 AC XY: 297103 AN XY: 727102

African (AFR) AF: 0.227 AC: 7611 AN: 33480

American (AMR) AF: 0.373 AC: 16695 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 9009 AN: 26136

East Asian (EAS) AF: 0.379 AC: 15036 AN: 39700

South Asian (SAS) AF: 0.468 AC: 40344 AN: 86258

European-Finnish (FIN) AF: 0.460 AC: 24539 AN: 53336

Middle Eastern (MID) AF: 0.357 AC: 2059 AN: 5768

European-Non Finnish (NFE) AF: 0.409 AC: 454438 AN: 1111862

Other (OTH) AF: 0.403 AC: 24306 AN: 60372

GnomAD4 genome AF: 0.359 AC: 54563 AN: 152106 Hom.: 10249 Cov.: 32 AF XY: 0.363 AC XY: 26937 AN XY: 74302

African (AFR) AF: 0.243 AC: 10106 AN: 41518

American (AMR) AF: 0.371 AC: 5673 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1175 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1927 AN: 5150

South Asian (SAS) AF: 0.469 AC: 2266 AN: 4828

European-Finnish (FIN) AF: 0.465 AC: 4902 AN: 10546

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27120 AN: 67986

Other (OTH) AF: 0.357 AC: 752 AN: 2108

Alfa AF: 0.380 Hom.: 23076

Bravo AF: 0.346

Asia WGS AF: 0.421 AC: 1458 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.393

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Adams-Oliver syndrome 2 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.17
DANN	Benign	0.74
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3745682; hg19: chr19-11313256; COSMIC: COSV53912511; COSMIC: COSV53912511;