19-11199430-C-T

Variant names:

• chr19-11199430-C-T
• rs78942291
• NM_020812.4:c.*67G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020812.4(DOCK6):​c.*67G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,543,122 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (45 hom.)
• Consequence: DOCK6 NM_020812.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.171

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 (MetaRNN=0.004704863).
• BP6: Variant 19-11199430-C-T is Benign according to our data. Variant chr19-11199430-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1707391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00406 (619/152388) while in subpopulation SAS AF= 0.0124 (60/4832). AF 95% confidence interval is 0.0099. There are 4 homozygotes in gnomad4. There are 278 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	c.*67G>A		3_prime_UTR_variant	Exon 48 of 48	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618	c.*67G>A		3_prime_UTR_variant	Exon 48 of 48	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587734.1	c.185G>A	p.Gly62Glu	missense_variant	Exon 2 of 2	5		ENSP00000468291.1
DOCK6	ENST00000586702.1	n.1114G>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
DOCK6	ENST00000587656.6	c.*67G>A		downstream_gene_variant		5		ENSP00000468638.2

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 619 AN: 152270 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00644

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00471 AC: 742 AN: 157612 Hom.: 6 AF XY: 0.00553 AC XY: 461 AN XY: 83344

Gnomad AFR exome AF: 0.000989

Gnomad AMR exome AF: 0.00198

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0126

Gnomad FIN exome AF: 0.000664

Gnomad NFE exome AF: 0.00609

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00654 AC: 9089 AN: 1390734 Hom.: 45 Cov.: 28 AF XY: 0.00663 AC XY: 4554 AN XY: 686578

Gnomad4 AFR exome AF: 0.000795

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0122

Gnomad4 FIN exome AF: 0.000547

Gnomad4 NFE exome AF: 0.00713

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.00406 AC: 619 AN: 152388 Hom.: 4 Cov.: 33 AF XY: 0.00373 AC XY: 278 AN XY: 74526

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00644

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00423 Hom.: 0

Bravo AF: 0.00363

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00289 AC: 4

ESP6500EA AF: 0.00817 AC: 26

ExAC AF: 0.00251 AC: 258

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DOCK6: BS1, BS2 -

Jul 18, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.46
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0047	T
MVP		0.63
GERP RS		-0.26

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: rs78942291; hg19: chr19-11310106;