rs6555882
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1
The NM_004946.3(DOCK2):āc.3828G>Cā(p.Leu1276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 1,613,438 control chromosomes in the GnomAD database, including 3,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.088 ( 1474 hom., cov: 32)
Exomes š: 0.024 ( 1719 hom. )
Consequence
DOCK2
NM_004946.3 synonymous
NM_004946.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.46
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 5-170042084-G-C is Benign according to our data. Variant chr5-170042084-G-C is described in ClinVar as [Benign]. Clinvar id is 476012.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=2.46 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.3828G>C | p.Leu1276= | synonymous_variant | 38/52 | ENST00000520908.7 | |
DOCK2 | NR_156756.1 | n.3931G>C | non_coding_transcript_exon_variant | 39/53 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.3828G>C | p.Leu1276= | synonymous_variant | 38/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0874 AC: 13291AN: 152002Hom.: 1467 Cov.: 32
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GnomAD3 exomes AF: 0.0368 AC: 9207AN: 250318Hom.: 669 AF XY: 0.0333 AC XY: 4502AN XY: 135304
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GnomAD4 exome AF: 0.0242 AC: 35348AN: 1461318Hom.: 1719 Cov.: 31 AF XY: 0.0243 AC XY: 17634AN XY: 726934
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GnomAD4 genome ? AF: 0.0876 AC: 13324AN: 152120Hom.: 1474 Cov.: 32 AF XY: 0.0847 AC XY: 6301AN XY: 74378
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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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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