rs149853735
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_004946.3(DOCK2):c.3417G>A(p.Glu1139=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
DOCK2
NM_004946.3 synonymous
NM_004946.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0930
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 -9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 5-170027898-G-A is Benign according to our data. Variant chr5-170027898-G-A is described in ClinVar as [Benign]. Clinvar id is 542630.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.093 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0013 (198/152328) while in subpopulation AFR AF= 0.00443 (184/41574). AF 95% confidence interval is 0.0039. There are 0 homozygotes in gnomad4. There are 91 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.3417G>A | p.Glu1139= | synonymous_variant | 34/52 | ENST00000520908.7 | |
DOCK2 | NR_156756.1 | n.3520G>A | non_coding_transcript_exon_variant | 35/53 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.3417G>A | p.Glu1139= | synonymous_variant | 34/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00130 AC: 198AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000315 AC: 79AN: 250822Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135566
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GnomAD4 exome AF: 0.000114 AC: 167AN: 1460986Hom.: 0 Cov.: 31 AF XY: 0.0000991 AC XY: 72AN XY: 726802
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GnomAD4 genome AF: 0.00130 AC: 198AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.00122 AC XY: 91AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DOCK2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
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