Variant X-118561497-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_144658.4(DOCK11):c.673G>T(p.Ala225Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,198,512 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 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: 3.21

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20280498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4 linkuse as main transcript	c.673G>T	p.Ala225Ser	missense_variant	7/53	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.673G>T	p.Ala225Ser	missense_variant	7/53	1	NM_144658.4	ENSP00000276202.7	Q5JSL3
DOCK11	ENST00000276204.10 linkuse as main transcript	c.673G>T	p.Ala225Ser	missense_variant	7/53	5		ENSP00000276204.6	A6NIW2
DOCK11	ENST00000633080.1 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	2/49	5		ENSP00000487829.1	A0A0J9YW64

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

111996

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34162

show subpopulations

Gnomad AFR

AF:

0.000130

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

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1086516

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

353178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000385

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.0000357

AC:

AN:

111996

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34162

show subpopulations

Gnomad4 AFR

AF:

0.000130

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:

0.0000151

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

Oct 12, 2021

The c.673G>T (p.A225S) alteration is located in exon 7 (coding exon 7) of the DOCK11 gene. This alteration results from a G to T substitution at nucleotide position 673, causing the alanine (A) at amino acid position 225 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

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.062

.;T;T

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.052

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-2.4

.;N;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

1.1

N;N;.

REVEL

Benign

0.27

Sift

Benign

0.65

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.081

.;B;.

Vest4

0.16

MutPred

0.46

Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);.;

MVP

0.45

MPC

0.34

ClinPred

0.61

GERP RS

5.4

Varity_R

0.12

gMVP

0.52

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