rs8101345

Variant names:

• chr19-11200244-C-T
• rs8101345
• NM_020812.4:c.6101+64G>A

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.6101+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 1,497,118 control chromosomes in the GnomAD database, including 144,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17246 hom., cov: 31)
  • Exomes 𝑓: 0.43 (127162 hom.)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.806
• Publications: 8 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=-0.9).
• BP6: Variant 19-11200244-C-T is Benign according to our data. Variant chr19-11200244-C-T is described in ClinVar as Benign. ClinVar VariationId is 1264914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 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.6101+64G>A		intron	N/A	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.6206+64G>A		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.6101+64G>A		intron	N/A	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587656.6	TSL:5	c.6206+64G>A		intron	N/A	ENSP00000468638.2	K7ESB7
	DOCK6	ENST00000587734.1	TSL:5	c.76-705G>A		intron	N/A	ENSP00000468291.1	K7ERK2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71450 AN: 151594 Hom.: 17215 Cov.: 31

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.432 AC: 581395 AN: 1345408 Hom.: 127162 AF XY: 0.433 AC XY: 285636 AN XY: 659948

African (AFR) AF: 0.575 AC: 17385 AN: 30256

American (AMR) AF: 0.469 AC: 14714 AN: 31404

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 7743 AN: 22434

East Asian (EAS) AF: 0.572 AC: 20164 AN: 35246

South Asian (SAS) AF: 0.495 AC: 36242 AN: 73190

European-Finnish (FIN) AF: 0.462 AC: 21883 AN: 47360

Middle Eastern (MID) AF: 0.389 AC: 1525 AN: 3918

European-Non Finnish (NFE) AF: 0.418 AC: 436931 AN: 1046028

Other (OTH) AF: 0.446 AC: 24808 AN: 55572

GnomAD4 genome AF: 0.472 AC: 71534 AN: 151710 Hom.: 17246 Cov.: 31 AF XY: 0.473 AC XY: 35061 AN XY: 74132

African (AFR) AF: 0.577 AC: 23817 AN: 41290

American (AMR) AF: 0.457 AC: 6963 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3472

East Asian (EAS) AF: 0.557 AC: 2880 AN: 5166

South Asian (SAS) AF: 0.513 AC: 2465 AN: 4806

European-Finnish (FIN) AF: 0.465 AC: 4881 AN: 10502

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27700 AN: 67920

Other (OTH) AF: 0.451 AC: 950 AN: 2106

Alfa AF: 0.442 Hom.: 1913

Bravo AF: 0.476

Asia WGS AF: 0.569 AC: 1972 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8101345; hg19: chr19-11310920;