Variant chr2-224774916-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014689.3(DOCK10):c.6002C>T(p.Thr2001Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,593,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

DOCK10
NM_014689.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

DOCK10 (HGNC:23479): (dedicator of cytokinesis 10) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family are guanosine nucleotide exchange factors for Rho GTPases and defined by the presence of conserved DOCK-homology regions. The encoded protein belongs to the D (or Zizimin) subfamily of DOCK proteins, which also contain an N-terminal pleckstrin homology domain. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Mar 2014]

DOCK10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK10	NM_014689.3 linkuse as main transcript	c.6002C>T	p.Thr2001Met	missense_variant	52/56	ENST00000258390.12	NP_055504.2	Q96BY6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK10	ENST00000258390.12 linkuse as main transcript	c.6002C>T	p.Thr2001Met	missense_variant	52/56	5	NM_014689.3	ENSP00000258390.7		Q96BY6-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.0000275

AC:

AN:

218220

Hom.:

AF XY:

0.0000255

AC XY:

AN XY:

117756

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000633

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1441042

Hom.:

Cov.:

AF XY:

0.00000979

AC XY:

AN XY:

714834

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000480

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000636

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000169

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:

0.0000453

ExAC

AF:

0.00000828

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3478

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

Dec 09, 2024

The c.6002C>T (p.T2001M) alteration is located in exon 52 (coding exon 52) of the DOCK10 gene. This alteration results from a C to T substitution at nucleotide position 6002, causing the threonine (T) at amino acid position 2001 to be replaced by a methionine (M). 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

0.30

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

.;T;.

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.6

.;H;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.9

D;D;.

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

.;D;.

Vest4

0.94

MutPred

0.78

.;Gain of MoRF binding (P = 0.06);.;

MVP

0.62

MPC

0.68

ClinPred

0.96

GERP RS

5.5

Varity_R

0.66

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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