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GeneBe

rs370911923

chr5-170081849-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_004946.3(DOCK2):c.5295G>A(p.Ala1765=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,610,990 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 0.00017 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

DOCK2
NM_004946.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.17
Variant links:
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
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-170081849-G-A is Benign according to our data. Variant chr5-170081849-G-A is described in ClinVar as [Benign]. Clinvar id is 476015.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.17 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000166 (25/150504) while in subpopulation AMR AF= 0.000463 (7/15116). AF 95% confidence interval is 0.000217. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DOCK2NM_004946.3 linkuse as main transcriptc.5295G>A p.Ala1765= synonymous_variant 51/52 ENST00000520908.7
DOCK2NR_156756.1 linkuse as main transcriptn.5398G>A non_coding_transcript_exon_variant 52/53

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DOCK2ENST00000520908.7 linkuse as main transcriptc.5295G>A p.Ala1765= synonymous_variant 51/522 NM_004946.3 P1Q92608-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000166
AC:
25
AN:
150504
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000491
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000463
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000392
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000332
AC:
83
AN:
250208
Hom.:
0
AF XY:
0.000274
AC XY:
37
AN XY:
135182
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00162
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000142
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.000155
AC:
226
AN:
1460486
Hom.:
0
Cov.:
34
AF XY:
0.000165
AC XY:
120
AN XY:
726540
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.00157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000929
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000112
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000166
AC:
25
AN:
150504
Hom.:
0
Cov.:
31
AF XY:
0.000123
AC XY:
9
AN XY:
73316
show subpopulations
Gnomad4 AFR
AF:
0.0000491
Gnomad4 AMR
AF:
0.000463
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000392
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.000264
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

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 submitterclinical testingInvitaeDec 22, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
0.11
Dann
Benign
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370911923; hg19: chr5-169508853; COSMIC: COSV56984604; API