rs3763048
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004946.3(DOCK2):c.3612C>T(p.Thr1204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,613,754 control chromosomes in the GnomAD database, including 114,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.43 ( 15154 hom., cov: 33)
Exomes 𝑓: 0.36 ( 98925 hom. )
Consequence
DOCK2
NM_004946.3 synonymous
NM_004946.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.00
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 5-170034543-C-T is Benign according to our data. Variant chr5-170034543-C-T is described in ClinVar as [Benign]. Clinvar id is 1165009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=-5 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.3612C>T | p.Thr1204= | synonymous_variant | 35/52 | ENST00000520908.7 | |
DOCK2 | NR_156756.1 | n.3715C>T | non_coding_transcript_exon_variant | 36/53 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.3612C>T | p.Thr1204= | synonymous_variant | 35/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.429 AC: 65149AN: 151956Hom.: 15138 Cov.: 33
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GnomAD3 exomes AF: 0.397 AC: 99645AN: 250920Hom.: 21024 AF XY: 0.396 AC XY: 53733AN XY: 135594
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GnomAD4 exome AF: 0.361 AC: 527089AN: 1461680Hom.: 98925 Cov.: 41 AF XY: 0.364 AC XY: 264313AN XY: 727130
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GnomAD4 genome ? AF: 0.429 AC: 65222AN: 152074Hom.: 15154 Cov.: 33 AF XY: 0.430 AC XY: 31984AN XY: 74324
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ClinVar
Significance: Benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DOCK2 deficiency Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. - |
not provided Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at