Genetic Variant DOCK6:c.*220G>A (chr19-11199277-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020812.4(DOCK6):c.*220G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 574,722 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 12 hom. )

Consequence

DOCK6
NM_020812.4 downstream_gene

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.605

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-11199277-C-T is Benign according to our data. Variant chr19-11199277-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1223545.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00586 (892/152224) while in subpopulation EAS AF= 0.0191 (99/5190). AF 95% confidence interval is 0.016. There are 4 homozygotes in gnomad4. There are 439 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4 link	c.*220G>A		downstream_gene_variant		ENST00000294618.12	NP_065863.2	Q96HP0B7Z9U8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DOCK6	ENST00000294618.12 link	c.*220G>A	downstream_gene_variant	1	NM_020812.4	ENSP00000294618.6	Q96HP0
DOCK6	ENST00000587656.6 link	c.*220G>A	downstream_gene_variant	5		ENSP00000468638.2	K7ESB7
DOCK6	ENST00000587734.1 link	c.*41G>A	downstream_gene_variant	5		ENSP00000468291.1	K7ERK2
DOCK6	ENST00000586702.1 link	n.*18G>A	downstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

891

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00911

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.0188

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00460

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00787

AC:

502

AN:

63798

Hom.:

AF XY:

0.00747

AC XY:

238

AN XY:

31848

show subpopulations

Gnomad AFR exome

AF:

0.00594

Gnomad AMR exome

AF:

0.00837

Gnomad ASJ exome

AF:

0.0247

Gnomad EAS exome

AF:

0.0212

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.000768

Gnomad NFE exome

AF:

0.00468

Gnomad OTH exome

AF:

0.00900

GnomAD4 exome

AF:

0.00546

AC:

2306

AN:

422498

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

1168

AN XY:

222204

show subpopulations

Gnomad4 AFR exome

AF:

0.00501

Gnomad4 AMR exome

AF:

0.00744

Gnomad4 ASJ exome

AF:

0.0231

Gnomad4 EAS exome

AF:

0.0157

Gnomad4 SAS exome

AF:

0.00210

Gnomad4 FIN exome

AF:

0.000485

Gnomad4 NFE exome

AF:

0.00429

Gnomad4 OTH exome

AF:

0.00683

GnomAD4 genome

AF:

0.00586

AC:

892

AN:

152224

Hom.:

Cov.:

AF XY:

0.00590

AC XY:

439

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00494

Gnomad4 AMR

AF:

0.00910

Gnomad4 ASJ

AF:

0.0268

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00460

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00621

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 13, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

DANN

Benign

0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over