rs34133853
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_004946.3(DOCK2):āc.3945T>Cā(p.Tyr1315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,614,150 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0091 ( 29 hom., cov: 32)
Exomes š: 0.00097 ( 20 hom. )
Consequence
DOCK2
NM_004946.3 synonymous
NM_004946.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.703
Genes affected
DOCK2 (HGNC:2988): (dedicator of cytokinesis 2) The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. Mutations in this gene result in immunodeficiency 40 (IMD40), a combined form of immunodeficiency that affects T cell number and function, also with variable defects in B cell and NK cell function. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 5-170045884-T-C is Benign according to our data. Variant chr5-170045884-T-C is described in ClinVar as [Benign]. Clinvar id is 476013.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.703 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00913 (1391/152290) while in subpopulation AFR AF= 0.0322 (1336/41554). AF 95% confidence interval is 0.0307. There are 29 homozygotes in gnomad4. There are 646 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 29 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.3945T>C | p.Tyr1315= | synonymous_variant | 39/52 | ENST00000520908.7 | NP_004937.1 | |
DOCK2 | NR_156756.1 | n.4048T>C | non_coding_transcript_exon_variant | 40/53 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.3945T>C | p.Tyr1315= | synonymous_variant | 39/52 | 2 | NM_004946.3 | ENSP00000429283 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00912 AC: 1388AN: 152172Hom.: 29 Cov.: 32
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GnomAD3 exomes AF: 0.00240 AC: 602AN: 251178Hom.: 10 AF XY: 0.00165 AC XY: 224AN XY: 135750
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GnomAD4 exome AF: 0.000968 AC: 1415AN: 1461860Hom.: 20 Cov.: 31 AF XY: 0.000785 AC XY: 571AN XY: 727234
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GnomAD4 genome AF: 0.00913 AC: 1391AN: 152290Hom.: 29 Cov.: 32 AF XY: 0.00868 AC XY: 646AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DOCK2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
DOCK2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 08, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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