Genetic Variant NM_020812.4:c.6066G>C (chr19-11200343-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_020812.4(DOCK6):c.6066G>C(p.Leu2022Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,576,564 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

DOCK6
NM_020812.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.15

Publications

2 publications found

Variant links:

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 links:

DOCK6-AS1 (HGNC:56684): (DOCK6 antisense RNA 1)

DOCK6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 19-11200343-C-G is Benign according to our data. Variant chr19-11200343-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1944528.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.15 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.6066G>C	p.Leu2022Leu	synonymous	Exon 47 of 48	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.6171G>C	p.Leu2057Leu	synonymous	Exon 48 of 49	NP_001354759.1	K7ESB7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DOCK6	ENST00000294618.12	TSL:1 MANE Select	c.6066G>C	p.Leu2022Leu	synonymous	Exon 47 of 48	ENSP00000294618.6	Q96HP0
DOCK6	ENST00000587656.6	TSL:5	c.6171G>C	p.Leu2057Leu	synonymous	Exon 48 of 49	ENSP00000468638.2	K7ESB7
DOCK6	ENST00000587734.1	TSL:5	c.76-804G>C		intron	N/A	ENSP00000468291.1	K7ERK2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000702

AC:

AN:

1424476

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

705186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32626

American (AMR)

AF:

0.00

AC:

AN:

38974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25476

East Asian (EAS)

AF:

0.00

AC:

AN:

37664

South Asian (SAS)

AF:

0.00

AC:

AN:

81218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.00000823

AC:

AN:

1093238

Other (OTH)

AF:

0.0000170

AC:

AN:

58978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

6.8

(source)

DANN

Benign

0.74

PhyloP100

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over