Variant 8-25292161-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024940.8(DOCK5):c.459T>A(p.Asp153Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,425,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

DOCK5
NM_024940.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680

Variant links:

Genes affected

DOCK5 (HGNC:23476): (dedicator of cytokinesis 5) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family act as guanine nucleotide exchange factors for small Rho family G proteins. The protein encoded by this gene is thought to associate with adaptors CRK and CRKL, and function in regulation of intestinal epithelial cell spreading and migration on collagen IV. Similar proteins in mouse and zebrafish also function in myoblast fusion. [provided by RefSeq, Oct 2016]

DOCK5 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
DOCK5	NM_024940.8 linkuse as main transcript	c.459T>A	p.Asp153Glu	missense_variant	6/52	ENST00000276440.12	NP_079216.4	Q9H7D0-1Q68DL4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK5	ENST00000276440.12 linkuse as main transcript	c.459T>A	p.Asp153Glu	missense_variant	6/52	1	NM_024940.8	ENSP00000276440.7		Q9H7D0-1
DOCK5	ENST00000481100.5 linkuse as main transcript	c.459T>A	p.Asp153Glu	missense_variant	6/11	1		ENSP00000429737.1		Q9H7D0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000151

AC:

AN:

198540

Hom.:

AF XY:

0.0000284

AC XY:

AN XY:

105556

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:

0.000124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000491

AC:

AN:

1425212

Hom.:

Cov.:

AF XY:

0.00000709

AC XY:

AN XY:

705494

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000868

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

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

Mar 16, 2024

The c.459T>A (p.D153E) alteration is located in exon 6 (coding exon 6) of the DOCK5 gene. This alteration results from a T to A substitution at nucleotide position 459, causing the aspartic acid (D) at amino acid position 153 to be replaced by a glutamic acid (E). 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

0.95

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.24

Sift

Benign

0.034

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.92

.;P

Vest4

0.95

MutPred

0.45

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.14

MPC

0.091

ClinPred

0.57

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.75

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