19-11199530-CAAG-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_020812.4(DOCK6):c.6108_6110del(p.Leu2037del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000886 in 1,580,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000084 ( 0 hom. )
Consequence
DOCK6
NM_020812.4 inframe_deletion
NM_020812.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.84
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a modified_residue Phosphoserine (size 0) in uniprot entity DOCK6_HUMAN
PM2
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Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_020812.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK6 | NM_020812.4 | c.6108_6110del | p.Leu2037del | inframe_deletion | 48/48 | ENST00000294618.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK6 | ENST00000294618.12 | c.6108_6110del | p.Leu2037del | inframe_deletion | 48/48 | 1 | NM_020812.4 | A2 | |
DOCK6 | ENST00000587656.6 | c.6213_6215del | p.Leu2072del | inframe_deletion | 49/49 | 5 | P3 | ||
DOCK6 | ENST00000587734.1 | c.82_84del | p.Leu28del | inframe_deletion | 2/2 | 5 | |||
DOCK6 | ENST00000586702.1 | n.1011_1013del | non_coding_transcript_exon_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000840 AC: 12AN: 1428344Hom.: 0 AF XY: 0.00000566 AC XY: 4AN XY: 706996
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 01, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with DOCK6-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.6108_6110del, results in the deletion of 1 amino acid(s) of the DOCK6 protein (p.Leu2037del), but otherwise preserves the integrity of the reading frame. - |
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at