rs737337

Variant names:

• chr19-11236817-T-C
• rs737337
• NM_020812.4:c.2136A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020812.4(DOCK6):​c.2136A>G​(p.Thr712Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,553,570 control chromosomes in the GnomAD database, including 15,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (4814 hom., cov: 32)
  • Exomes 𝑓: 0.10 (10987 hom.)
• Consequence: DOCK6 NM_020812.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.24
• Publications: 113 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 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Adams-Oliver syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-11236817-T-C is Benign according to our data. Variant chr19-11236817-T-C is described in ClinVar as [Benign]. Clinvar id is 1170730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK6	NM_020812.4	c.2136A>G	p.Thr712Thr	synonymous_variant	Exon 19 of 48	ENST00000294618.12	NP_065863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK6	ENST00000294618.12	c.2136A>G	p.Thr712Thr	synonymous_variant	Exon 19 of 48	1	NM_020812.4	ENSP00000294618.6
DOCK6	ENST00000587656.6	c.2136A>G	p.Thr712Thr	synonymous_variant	Exon 19 of 49	5		ENSP00000468638.2
DOCK6	ENST00000590680.5	c.477A>G	p.Thr159Thr	synonymous_variant	Exon 5 of 11	5		ENSP00000467191.1
DOCK6	ENST00000591750.1	n.2105A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30275 AN: 151990 Hom.: 4799 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0830

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.151 AC: 23987 AN: 158802 AF XY: 0.141

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.0894

Gnomad NFE exome AF: 0.0779

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.101 AC: 142035 AN: 1401462 Hom.: 10987 Cov.: 32 AF XY: 0.102 AC XY: 70294 AN XY: 691542

African (AFR) AF: 0.447 AC: 14129 AN: 31640

American (AMR) AF: 0.272 AC: 9747 AN: 35858

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 701 AN: 25228

East Asian (EAS) AF: 0.264 AC: 9471 AN: 35914

South Asian (SAS) AF: 0.150 AC: 11887 AN: 79272

European-Finnish (FIN) AF: 0.0900 AC: 4413 AN: 49032

Middle Eastern (MID) AF: 0.0936 AC: 533 AN: 5696

European-Non Finnish (NFE) AF: 0.0782 AC: 84540 AN: 1080732

Other (OTH) AF: 0.114 AC: 6614 AN: 58090

GnomAD4 genome AF: 0.199 AC: 30342 AN: 152108 Hom.: 4814 Cov.: 32 AF XY: 0.201 AC XY: 14942 AN XY: 74378

African (AFR) AF: 0.429 AC: 17781 AN: 41462

American (AMR) AF: 0.221 AC: 3379 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1314 AN: 5166

South Asian (SAS) AF: 0.157 AC: 758 AN: 4824

European-Finnish (FIN) AF: 0.0847 AC: 899 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0830 AC: 5643 AN: 67964

Other (OTH) AF: 0.170 AC: 359 AN: 2114

Alfa AF: 0.117 Hom.: 8002

Bravo AF: 0.223

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.42
PhyloP100		-3.2
PromoterAI		0.0088	Neutral
Mutation Taster		=92/8	polymorphism (auto)

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: rs737337; hg19: chr19-11347493; COSMIC: COSV52948838; COSMIC: COSV52948838;