chr19-11199430-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

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.*67G>A		3_prime_UTR	Exon 48 of 48	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.*67G>A		3_prime_UTR	Exon 49 of 49	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.*67G>A		3_prime_UTR	Exon 48 of 48	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587734.1	TSL:5	c.185G>A	p.Gly62Glu	missense	Exon 2 of 2	ENSP00000468291.1	K7ERK2
	DOCK6	ENST00000586702.1	TSL:2	n.1114G>A		non_coding_transcript_exon	Exon 7 of 7

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

GnomAD2 exomes AF: 0.00471 AC: 742 AN: 157612 AF XY: 0.00553

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 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

African (AFR) AF: 0.000795 AC: 25 AN: 31462

American (AMR) AF: 0.00221 AC: 79 AN: 35742

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25160

East Asian (EAS) AF: 0.00 AC: 0 AN: 35784

South Asian (SAS) AF: 0.0122 AC: 966 AN: 79008

European-Finnish (FIN) AF: 0.000547 AC: 27 AN: 49356

Middle Eastern (MID) AF: 0.00360 AC: 20 AN: 5562

European-Non Finnish (NFE) AF: 0.00713 AC: 7631 AN: 1070870

Other (OTH) AF: 0.00588 AC: 340 AN: 57790

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

African (AFR) AF: 0.00137 AC: 57 AN: 41600

American (AMR) AF: 0.00314 AC: 48 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0124 AC: 60 AN: 4832

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00644 AC: 438 AN: 68038

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00342 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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
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
PhyloP100		-0.17
MVP		0.63
GERP RS		-0.26
Mutation Taster		=100/0	polymorphism

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: rs78942291; hg19: chr19-11310106;