19-11200244-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.806

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 -14 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 id is 1264914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK6	NM_020812.4	c.6101+64G>A		intron_variant		ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK6	ENST00000294618.12	c.6101+64G>A		intron_variant		1	NM_020812.4	A2
DOCK6	ENST00000587656.6	c.6206+64G>A		intron_variant		5		P3
DOCK6	ENST00000587734.1	c.76-705G>A		intron_variant		5
DOCK6	ENST00000586702.1	n.1004+64G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.572

Gnomad4 SAS exome AF: 0.495

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.446

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

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.451

Alfa AF: 0.442 Hom.: 1913

Bravo AF: 0.476

Asia WGS AF: 0.569 AC: 1972 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.9
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs8101345; hg19: chr19-11310920;