Variant X-118572441-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_144658.4(DOCK11):c.1154A>G(p.Asn385Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000665 in 1,203,105 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

DOCK11
NM_144658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

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=0.09384671).

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4 linkuse as main transcript	c.1154A>G	p.Asn385Ser	missense_variant	11/53	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.1154A>G	p.Asn385Ser	missense_variant	11/53	1	NM_144658.4	ENSP00000276202.7	Q5JSL3
DOCK11	ENST00000276204.10 linkuse as main transcript	c.1154A>G	p.Asn385Ser	missense_variant	11/53	5		ENSP00000276204.6	A6NIW2
DOCK11	ENST00000633080.1 linkuse as main transcript	c.602A>G	p.Asn201Ser	missense_variant	6/49	5		ENSP00000487829.1	A0A0J9YW64

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111583

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33757

show subpopulations

Gnomad AFR

AF:

0.000196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000552

AC:

AN:

181082

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65620

show subpopulations

Gnomad AFR exome

AF:

0.0000764

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1091522

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

357476

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111583

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33757

show subpopulations

Gnomad4 AFR

AF:

0.000196

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.1154A>G (p.N385S) alteration is located in exon 11 (coding exon 11) of the DOCK11 gene. This alteration results from a A to G substitution at nucleotide position 1154, causing the asparagine (N) at amino acid position 385 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.92

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;T;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.035

.;N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.066

Sift

Benign

0.22

T;T;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.11

MutPred

0.32

Gain of glycosylation at N385 (P = 0.0697);Gain of glycosylation at N385 (P = 0.0697);.;

MVP

0.29

MPC

0.28

ClinPred

0.26

GERP RS

4.3

Varity_R

0.14

gMVP

0.10

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