19-11252470-A-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_020812.4(DOCK6):c.377+12T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 1,613,360 control chromosomes in the GnomAD database, including 434,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.61 ( 31568 hom., cov: 32)
Exomes 𝑓: 0.74 ( 403226 hom. )
Consequence
DOCK6
NM_020812.4 intron
NM_020812.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.595
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 19-11252470-A-T is Benign according to our data. Variant chr19-11252470-A-T is described in ClinVar as [Benign]. Clinvar id is 261356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11252470-A-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK6 | NM_020812.4 | c.377+12T>A | intron_variant | ENST00000294618.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK6 | ENST00000294618.12 | c.377+12T>A | intron_variant | 1 | NM_020812.4 | A2 | |||
DOCK6 | ENST00000587656.6 | c.377+12T>A | intron_variant | 5 | P3 | ||||
DOCK6 | ENST00000585609.1 | n.662T>A | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
DOCK6 | ENST00000586482.1 | n.286T>A | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.609 AC: 92586AN: 151950Hom.: 31559 Cov.: 32
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GnomAD3 exomes AF: 0.699 AC: 173969AN: 248786Hom.: 62796 AF XY: 0.714 AC XY: 96373AN XY: 135060
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GnomAD4 exome AF: 0.738 AC: 1078642AN: 1461292Hom.: 403226 Cov.: 49 AF XY: 0.741 AC XY: 538319AN XY: 726932
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GnomAD4 genome AF: 0.609 AC: 92632AN: 152068Hom.: 31568 Cov.: 32 AF XY: 0.610 AC XY: 45323AN XY: 74328
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Adams-Oliver syndrome 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 16, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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