19-11252470-A-T

Variant names:

• chr19-11252470-A-T
• rs8113582
• NM_020812.4:c.377+12T>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020812.4(DOCK6):​c.377+12T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,613,360 control chromosomes in the GnomAD database, including 434,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (31568 hom., cov: 32)
  • Exomes 𝑓: 0.74 (403226 hom.)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.595

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-11252470-A-T is Benign according to our data. Variant chr19-11252470-A-T is described in ClinVar as [Benign]. Clinvar id is 261356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11252470-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.377+12T>A		intron_variant	Intron 4 of 47	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.377+12T>A		intron_variant	Intron 4 of 47	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587656.6	c.377+12T>A		intron_variant	Intron 4 of 48	5		ENSP00000468638.2
DOCK6	ENST00000585609.1	n.662T>A		non_coding_transcript_exon_variant	Exon 3 of 4	2
DOCK6	ENST00000586482.1	n.286T>A		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92586 AN: 151950 Hom.: 31559 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.660

GnomAD3 exomes AF: 0.699 AC: 173969 AN: 248786 Hom.: 62796 AF XY: 0.714 AC XY: 96373 AN XY: 135060

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.629

Gnomad ASJ exome AF: 0.773

Gnomad EAS exome AF: 0.649

Gnomad SAS exome AF: 0.744

Gnomad FIN exome AF: 0.730

Gnomad NFE exome AF: 0.762

Gnomad OTH exome AF: 0.751

GnomAD4 exome AF: 0.738 AC: 1078642 AN: 1461292 Hom.: 403226 Cov.: 49 AF XY: 0.741 AC XY: 538319 AN XY: 726932

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.636

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.743

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.759

Gnomad4 OTH exome AF: 0.721

GnomAD4 genome AF: 0.609 AC: 92632 AN: 152068 Hom.: 31568 Cov.: 32 AF XY: 0.610 AC XY: 45323 AN XY: 74328

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.663

Alfa AF: 0.694 Hom.: 7125

Bravo AF: 0.586

Asia WGS AF: 0.709 AC: 2464 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Adams-Oliver syndrome 2 Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: 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	-0.87
CADD	Benign	0.71
DANN	Benign	0.48
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs8113582; hg19: chr19-11363146; COSMIC: COSV53912530; COSMIC: COSV53912530;