chr19-11200159-AC-A

Variant names:

• chr19-11200159-AC-A
• rs377752825
• NM_020812.4:c.6101+148delG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020812.4(DOCK6):​c.6101+148delG 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
• Publications: 1 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 -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 VariationId 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.

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+148delG		intron	N/A	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.6206+148delG		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+148delG		intron	N/A	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587656.6	TSL:5	c.6206+148delG		intron	N/A	ENSP00000468638.2	K7ESB7
	DOCK6	ENST00000587734.1	TSL:5	c.76-621delG		intron	N/A	ENSP00000468291.1	K7ERK2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.133 AC: 1375 AN: 10322

American (AMR) AF: 0.133 AC: 1454 AN: 10938

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 791 AN: 10810

East Asian (EAS) AF: 0.200 AC: 3623 AN: 18128

South Asian (SAS) AF: 0.154 AC: 4277 AN: 27684

European-Finnish (FIN) AF: 0.101 AC: 2129 AN: 21148

Middle Eastern (MID) AF: 0.0809 AC: 148 AN: 1830

European-Non Finnish (NFE) AF: 0.0737 AC: 29878 AN: 405348

Other (OTH) AF: 0.0957 AC: 2278 AN: 23800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0658 AC: 2565 AN: 38964

American (AMR) AF: 0.0687 AC: 986 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 177 AN: 3420

East Asian (EAS) AF: 0.205 AC: 959 AN: 4674

South Asian (SAS) AF: 0.0829 AC: 379 AN: 4572

European-Finnish (FIN) AF: 0.0308 AC: 289 AN: 9384

Middle Eastern (MID) AF: 0.0909 AC: 24 AN: 264

European-Non Finnish (NFE) AF: 0.0698 AC: 4614 AN: 66070

Other (OTH) AF: 0.0631 AC: 125 AN: 1982

Alfa AF: 0.0197 Hom.: 10

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2
Mutation Taster		=21/79	disease causing (long InDel)

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

Other links and lift over

dbSNP: rs377752825; hg19: chr19-11310835;