dbSNP rs2840: DOK5:c.*558G>A (chr20-54651037-G-A) – 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.*558G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,192 control chromosomes in the GnomAD database, including 3,540 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 0.21 ( 3539 hom., cov: 33)

Exomes 𝑓: 0.16 ( 1 hom. )

Consequence

DOK5
NM_018431.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

5 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5 link	c.*558G>A	3_prime_UTR_variant	Exon 8 of 8	ENST00000262593.10	NP_060901.2	Q9P104-1
DOK5	NM_177959.3 link	c.*558G>A	3_prime_UTR_variant	Exon 8 of 8		NP_808874.1	Q9P104-2
DOK5	XM_024451946.2 link	c.*558G>A	3_prime_UTR_variant	Exon 8 of 8		XP_024307714.1
DOK5	XM_011528904.2 link	c.*558G>A	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.*558G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_018431.5	ENSP00000262593.5		Q9P104-1
DOK5	ENST00000395939.5 link	c.*558G>A		downstream_gene_variant		1		ENSP00000379270.1		Q9P104-2

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31701

AN:

152012

Hom.:

3527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.161

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.209

AC:

31742

AN:

152130

Hom.:

3539

Cov.:

AF XY:

0.204

AC XY:

15176

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.201

AC:

8341

AN:

41484

American (AMR)

AF:

0.281

AC:

4301

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

503

AN:

3472

East Asian (EAS)

AF:

0.00212

AC:

AN:

5178

South Asian (SAS)

AF:

0.143

AC:

691

AN:

4822

European-Finnish (FIN)

AF:

0.182

AC:

1930

AN:

10584

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15326

AN:

67984

Other (OTH)

AF:

0.207

AC:

437

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1295

2590

3885

5180

6475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.222

Hom.:

578

Bravo

AF:

0.218

Asia WGS

AF:

0.0850

AC:

300

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.091

(source)

DANN

Benign

0.58

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over