Genetic Variant DOCK5:p.Asp153Glu (chr8-25292161-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024940.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK5	NM_024940.8	MANE Select	c.459T>A	p.Asp153Glu	missense	Exon 6 of 52	NP_079216.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK5	ENST00000276440.12	TSL:1 MANE Select	c.459T>A	p.Asp153Glu	missense	Exon 6 of 52	ENSP00000276440.7	Q9H7D0-1
	DOCK5	ENST00000481100.5	TSL:1	c.459T>A	p.Asp153Glu	missense	Exon 6 of 11	ENSP00000429737.1	Q9H7D0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000151

AC:

AN:

198540

AF XY:

0.0000284

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 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

African (AFR)

AF:

0.00

AC:

AN:

32518

American (AMR)

AF:

0.00

AC:

AN:

38716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25228

East Asian (EAS)

AF:

0.00

AC:

AN:

38174

South Asian (SAS)

AF:

0.0000868

AC:

AN:

80672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095172

Other (OTH)

AF:

0.00

AC:

AN:

59220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.068

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.24

Sift

Benign

0.034

Sift4G

Pathogenic

0.0

Polyphen

0.92

Vest4

0.95

MutPred

0.45

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

Mutation Taster

=77/23

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over