19-11200159-AC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020812.4(DOCK6):c.6101+148del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 674,588 control chromosomes in the GnomAD database, including 1,010 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (496 hom., cov: 25)
  • Exomes 𝑓: 0.087 (514 hom.)
• Consequence: DOCK6 NM_020812.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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 -10 ACMG points.

• BP6: Variant 19-11200159-AC-A is Benign according to our data. Variant chr19-11200159-AC-A is described in ClinVar as [Benign]. Clinvar id is 1268615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK6	NM_020812.4	c.6101+148del		intron_variant		ENST00000294618.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK6	ENST00000294618.12	c.6101+148del		intron_variant		1	NM_020812.4	A2
DOCK6	ENST00000587656.6	c.6206+148del		intron_variant		5		P3
DOCK6	ENST00000587734.1	c.76-621del		intron_variant		5
DOCK6	ENST00000586702.1	n.1004+148del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10181 AN: 144528 Hom.: 497 Cov.: 25

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0909

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.0600

GnomAD4 exome AF: 0.0867 AC: 45953 AN: 530008 Hom.: 514 AF XY: 0.0892 AC XY: 23491 AN XY: 263294

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0737

Gnomad4 OTH exome AF: 0.0957

GnomAD4 genome AF: 0.0705 AC: 10190 AN: 144580 Hom.: 496 Cov.: 25 AF XY: 0.0695 AC XY: 4890 AN XY: 70326

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0518

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.0829

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.0631

Alfa AF: 0.0197 Hom.: 10

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

Aug 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs377752825; hg19: chr19-11310835;