Genetic Variant DOK5:c.*93C>G (chr20-54650572-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018431.5(DOK5):c.*93C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,227,530 control chromosomes in the GnomAD database, including 4,862 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 2689 hom., cov: 33)

Exomes 𝑓: 0.036 ( 2173 hom. )

Consequence

DOK5
NM_018431.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

14 publications found

Variant links:

Genes affected

DOK5 (HGNC:16173): (docking protein 5) The protein encoded by this gene is a member of the DOK family of membrane proteins, which are adapter proteins involved in signal transduction. The encoded protein interacts with phosphorylated receptor tyrosine kinases to mediate neurite outgrowth and activation of the MAP kinase pathway. Unlike other DOK family proteins, this protein does not interact with RASGAP. This protein is up-regulated in patients with systemic sclerosis and is associated with fibrosis induced by insulin-like growth factor binding protein 5. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2014]

DOK5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5 link	c.*93C>G	3_prime_UTR_variant	Exon 8 of 8	ENST00000262593.10	NP_060901.2	Q9P104-1
DOK5	NM_177959.3 link	c.*93C>G	3_prime_UTR_variant	Exon 8 of 8		NP_808874.1	Q9P104-2
DOK5	XM_024451946.2 link	c.*93C>G	3_prime_UTR_variant	Exon 8 of 8		XP_024307714.1
DOK5	XM_011528904.2 link	c.*93C>G	3_prime_UTR_variant	Exon 8 of 8		XP_011527206.1	Q9P104-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10 link	c.*93C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_018431.5	ENSP00000262593.5		Q9P104-1
DOK5	ENST00000395939.5 link	c.*93C>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000379270.1		Q9P104-2

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18318

AN:

152092

Hom.:

2685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0589

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0323

Gnomad OTH

AF:

0.106

GnomAD4 exome

AF:

0.0362

AC:

38958

AN:

1075320

Hom.:

2173

Cov.:

AF XY:

0.0344

AC XY:

18804

AN XY:

546048

show subpopulations

African (AFR)

AF:

0.351

AC:

8578

AN:

24410

American (AMR)

AF:

0.0421

AC:

1485

AN:

35270

Ashkenazi Jewish (ASJ)

AF:

0.0261

AC:

578

AN:

22152

East Asian (EAS)

AF:

0.000109

AC:

AN:

36840

South Asian (SAS)

AF:

0.0171

AC:

1230

AN:

71832

European-Finnish (FIN)

AF:

0.0195

AC:

906

AN:

46344

Middle Eastern (MID)

AF:

0.0494

AC:

247

AN:

5002

European-Non Finnish (NFE)

AF:

0.0301

AC:

23670

AN:

786382

Other (OTH)

AF:

0.0480

AC:

2260

AN:

47088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1645

3289

4934

6578

8223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

844

1688

2532

3376

4220

<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

AF:

0.120

AC:

18341

AN:

152210

Hom.:

2689

Cov.:

AF XY:

0.116

AC XY:

8667

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.352

AC:

14596

AN:

41484

American (AMR)

AF:

0.0587

AC:

898

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0137

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0184

AC:

195

AN:

10618

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0323

AC:

2198

AN:

68020

Other (OTH)

AF:

0.106

AC:

223

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

675

1349

2024

2698

3373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0795

Hom.:

192

Bravo

AF:

0.135

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.39

(source)

DANN

Benign

0.33

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over