Genetic Variant NM_004946.3:c.22G>A (chr5-169637348-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004946.3(DOCK2):c.22G>A(p.Asp8Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DOCK2
NM_004946.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Publications

0 publications found

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]

DOCK2 Gene-Disease associations (from GenCC):

DOCK2 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

DOCK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1395872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004946.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK2	NM_004946.3	MANE Select	c.22G>A	p.Asp8Asn	missense	Exon 1 of 52	NP_004937.1	Q92608-1
	DOCK2	NR_156756.1		n.74G>A		non_coding_transcript_exon	Exon 1 of 53

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DOCK2	ENST00000520908.7	TSL:2 MANE Select	c.22G>A	p.Asp8Asn	missense	Exon 1 of 52	ENSP00000429283.3	Q92608-1
DOCK2	ENST00000524185.5	TSL:1	n.22G>A		non_coding_transcript_exon	Exon 1 of 53	ENSP00000428850.1	E5RFJ0
DOCK2	ENST00000961039.1		c.22G>A	p.Asp8Asn	missense	Exon 1 of 52	ENSP00000631098.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1281322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

628048

African (AFR)

AF:

0.00

AC:

AN:

26076

American (AMR)

AF:

0.00

AC:

AN:

20688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20872

East Asian (EAS)

AF:

0.00

AC:

AN:

27968

South Asian (SAS)

AF:

0.00

AC:

AN:

66528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5184

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1026914

Other (OTH)

AF:

0.00

AC:

AN:

52786

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

DOCK2 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.081

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

M_CAP

Benign

0.0053

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.49

PhyloP100

2.7

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.3

REVEL

Benign

0.077

Sift

Benign

0.34

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.28

MutPred

0.32

Gain of MoRF binding (P = 0.0266)

MVP

0.37

MPC

0.69

ClinPred

0.68

GERP RS

5.2

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.28

gMVP

0.16

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over