Variant X-118566060-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_144658.4(DOCK11):c.749A>G(p.His250Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,209,647 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 75 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00016 ( 0 hom. 68 hem. )

Consequence

DOCK11
NM_144658.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.74

Variant links:

Genes affected

DOCK11 (HGNC:23483): (dedicator of cytokinesis 11) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including marginal zone B cell differentiation; positive regulation of GTPase activity; and positive regulation of filopodium assembly. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DOCK11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32992032).

BP6

Variant X-118566060-A-G is Benign according to our data. Variant chrX-118566060-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2661266.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4 linkuse as main transcript	c.749A>G	p.His250Arg	missense_variant	8/53	ENST00000276202.9	NP_653259.3	Q5JSL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DOCK11	ENST00000276202.9 linkuse as main transcript	c.749A>G	p.His250Arg	missense_variant	8/53	1	NM_144658.4	ENSP00000276202.7	Q5JSL3
DOCK11	ENST00000276204.10 linkuse as main transcript	c.749A>G	p.His250Arg	missense_variant	8/53	5		ENSP00000276204.6	A6NIW2
DOCK11	ENST00000633080.1 linkuse as main transcript	c.197A>G	p.His66Arg	missense_variant	3/49	5		ENSP00000487829.1	A0A0J9YW64

Frequencies

GnomAD3 genomes

AF:

0.000232

AC:

AN:

112181

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

34309

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000213

AC:

AN:

183073

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

67559

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000428

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000160

AC:

176

AN:

1097466

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

AN XY:

362870

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.000195

GnomAD4 genome

AF:

0.000232

AC:

AN:

112181

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

34309

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000378

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000328

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.749A>G (p.H250R) alteration is located in exon 8 (coding exon 8) of the DOCK11 gene. This alteration results from a A to G substitution at nucleotide position 749, causing the histidine (H) at amino acid position 250 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

DOCK11: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

.;T;T

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.97

D;D;D

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.5

D;D;.

REVEL

Uncertain

0.53

Sift

Benign

0.054

T;T;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.94

P;P;.

Vest4

0.47

MVP

0.66

MPC

1.3

ClinPred

0.16

GERP RS

5.5

Varity_R

0.64

gMVP

0.93

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over