rs35887608
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_004946.3(DOCK2):āc.2241T>Cā(p.Ile747=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,613,748 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.010 ( 27 hom., cov: 32)
Exomes š: 0.0012 ( 28 hom. )
Consequence
DOCK2
NM_004946.3 synonymous
NM_004946.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.13
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 5-169718765-T-C is Benign according to our data. Variant chr5-169718765-T-C is described in ClinVar as [Benign]. Clinvar id is 476006.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.13 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1572/152338) while in subpopulation AFR AF= 0.0357 (1483/41570). AF 95% confidence interval is 0.0342. There are 27 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 27 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.2241T>C | p.Ile747= | synonymous_variant | 22/52 | ENST00000520908.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.2241T>C | p.Ile747= | synonymous_variant | 22/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0103 AC: 1566AN: 152220Hom.: 27 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1566
AN:
152220
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00279 AC: 701AN: 251042Hom.: 10 AF XY: 0.00206 AC XY: 280AN XY: 135668
GnomAD3 exomes
AF:
AC:
701
AN:
251042
Hom.:
AF XY:
AC XY:
280
AN XY:
135668
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00121 AC: 1772AN: 1461410Hom.: 28 Cov.: 30 AF XY: 0.00107 AC XY: 776AN XY: 727008
GnomAD4 exome
AF:
AC:
1772
AN:
1461410
Hom.:
Cov.:
30
AF XY:
AC XY:
776
AN XY:
727008
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0103 AC: 1572AN: 152338Hom.: 27 Cov.: 32 AF XY: 0.00987 AC XY: 735AN XY: 74494
GnomAD4 genome
?
AF:
AC:
1572
AN:
152338
Hom.:
Cov.:
32
AF XY:
AC XY:
735
AN XY:
74494
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
11
AN:
3476
EpiCase
AF:
EpiControl
AF:
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
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at