NM_020812.4:c.6039T>C

Variant names:

• chr19-11200370-A-G
• rs1204283106
• NM_020812.4:c.6039T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_020812.4(DOCK6):​c.6039T>C​(p.Ala2013Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,441,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DOCK6 NM_020812.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.40
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-11200370-A-G is Benign according to our data. Variant chr19-11200370-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2893562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.4 with no splicing effect.

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.6039T>C	p.Ala2013Ala	synonymous	Exon 47 of 48	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.6144T>C	p.Ala2048Ala	synonymous	Exon 48 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.6039T>C	p.Ala2013Ala	synonymous	Exon 47 of 48	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587656.6	TSL:5	c.6144T>C	p.Ala2048Ala	synonymous	Exon 48 of 49	ENSP00000468638.2	K7ESB7
	DOCK6	ENST00000587734.1	TSL:5	c.76-831T>C		intron	N/A	ENSP00000468291.1	K7ERK2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215634 AF XY: 0.00000853

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000105

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1441826 Hom.: 0 Cov.: 32 AF XY: 0.00000419 AC XY: 3 AN XY: 715464

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

African (AFR) AF: 0.00 AC: 0 AN: 32988

American (AMR) AF: 0.00 AC: 0 AN: 41850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25714

East Asian (EAS) AF: 0.00 AC: 0 AN: 38628

South Asian (SAS) AF: 0.00 AC: 0 AN: 82806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102648

Other (OTH) AF: 0.0000168 AC: 1 AN: 59638

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00462622), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-3.4

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: rs1204283106; hg19: chr19-11311046;