Variant X-118561443-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144658.4(DOCK11):c.619T>C(p.Ser207Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,168 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

DOCK11
NM_144658.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4 link	c.619T>C	p.Ser207Pro	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 link	c.619T>C	p.Ser207Pro	missense_variant	7/53	1	NM_144658.4	ENSP00000276202.7	Q5JSL3
DOCK11	ENST00000276204.10 link	c.619T>C	p.Ser207Pro	missense_variant	7/53	5		ENSP00000276204.6	A6NIW2
DOCK11	ENST00000633080.1 link	c.67T>C	p.Ser23Pro	missense_variant	2/49	5		ENSP00000487829.1	A0A0J9YW64

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000568

AC:

AN:

176103

Hom.:

AF XY:

0.00

AC XY:

AN XY:

60907

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000389

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:

1093168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000579

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000416

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 24, 2024

The c.619T>C (p.S207P) alteration is located in exon 7 (coding exon 7) of the DOCK11 gene. This alteration results from a T to C substitution at nucleotide position 619, causing the serine (S) at amino acid position 207 to be replaced by a proline (P). 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Uncertain

0.028

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

N;N;.

REVEL

Uncertain

0.64

Sift

Uncertain

0.0040

D;D;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.63

MutPred

0.69

Gain of catalytic residue at S207 (P = 0.0248);Gain of catalytic residue at S207 (P = 0.0248);.;

MVP

0.68

MPC

1.3

ClinPred

0.61

GERP RS

5.4

Varity_R

0.85

gMVP

0.98

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.

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