rs397509398
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_020812.4(DOCK6):c.2520dupT(p.Arg841SerfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,602,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
DOCK6
NM_020812.4 frameshift
NM_020812.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.33
Publications
3 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 syndromeInheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- Adams-Oliver syndrome 2Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-11235631-G-GA is Pathogenic according to our data. Variant chr19-11235631-G-GA is described in ClinVar as Pathogenic. ClinVar VariationId is 55814.Status of the report is no_assertion_criteria_provided, 0 stars.
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
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DOCK6 | NM_020812.4 | MANE Select | c.2520dupT | p.Arg841SerfsTer6 | frameshift | Exon 21 of 48 | NP_065863.2 | ||
| DOCK6 | NM_001367830.1 | c.2520dupT | p.Arg841SerfsTer6 | frameshift | Exon 21 of 49 | NP_001354759.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DOCK6 | ENST00000294618.12 | TSL:1 MANE Select | c.2520dupT | p.Arg841SerfsTer6 | frameshift | Exon 21 of 48 | ENSP00000294618.6 | ||
| DOCK6 | ENST00000587656.6 | TSL:5 | c.2520dupT | p.Arg841SerfsTer6 | frameshift | Exon 21 of 49 | ENSP00000468638.2 | ||
| DOCK6 | ENST00000590680.5 | TSL:5 | c.861dupT | p.Arg288fs | frameshift | Exon 7 of 11 | ENSP00000467191.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152170
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
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Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1450280Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 719922 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1450280
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
719922
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33284
American (AMR)
AF:
AC:
0
AN:
43146
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25894
East Asian (EAS)
AF:
AC:
0
AN:
39298
South Asian (SAS)
AF:
AC:
0
AN:
84026
European-Finnish (FIN)
AF:
AC:
0
AN:
52692
Middle Eastern (MID)
AF:
AC:
1
AN:
5750
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106238
Other (OTH)
AF:
AC:
0
AN:
59952
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
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2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152170
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74332
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41462
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
1
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68026
Other (OTH)
AF:
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Adams-Oliver syndrome 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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