dbSNP rs2841: DOK5:c.*575G>A (chr20-54651054-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.*575G>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 0.301 in 152,164 control chromosomes in the GnomAD database, including 8,399 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 0.30 ( 8399 hom., cov: 33)

Exomes 𝑓: 0.29 ( 0 hom. )

Consequence

DOK5
NM_018431.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0670

Publications

11 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
DOK5	NM_018431.5 link	c.*575G>A	3_prime_UTR_variant	Exon 8 of 8	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3 link	c.*575G>A	3_prime_UTR_variant	Exon 8 of 8		NP_808874.1
DOK5	XM_024451946.2 link	c.*575G>A	3_prime_UTR_variant	Exon 8 of 8		XP_024307714.1
DOK5	XM_011528904.2 link	c.*575G>A	3_prime_UTR_variant	Exon 8 of 8		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10 link	c.*575G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5 link	c.*575G>A		downstream_gene_variant		1		ENSP00000379270.1

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45826

AN:

152018

Hom.:

8396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.286

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.292

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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

AF:

0.301

AC:

45826

AN:

152136

Hom.:

8399

Cov.:

AF XY:

0.306

AC XY:

22793

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0772

AC:

3205

AN:

41514

American (AMR)

AF:

0.330

AC:

5046

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1495

AN:

3470

East Asian (EAS)

AF:

0.439

AC:

2263

AN:

5156

South Asian (SAS)

AF:

0.367

AC:

1771

AN:

4828

European-Finnish (FIN)

AF:

0.425

AC:

4500

AN:

10582

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26299

AN:

67984

Other (OTH)

AF:

0.333

AC:

703

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1552

3104

4656

6208

7760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.297

Hom.:

4375

Bravo

AF:

0.283

Asia WGS

AF:

0.407

AC:

1414

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.9

(source)

DANN

Benign

0.72

PhyloP100

0.067

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over