dbSNP rs2842: DOK5:c.*564G>A (chr20-54651043-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.*564G>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 0.545 in 152,102 control chromosomes in the GnomAD database, including 22,763 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 0.54 ( 22754 hom., cov: 33)

Exomes 𝑓: 0.50 ( 9 hom. )

Consequence

DOK5
NM_018431.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.445

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=-0.91).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018431.5. 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
	DOK5	NM_018431.5	MANE Select	c.*564G>A		3_prime_UTR	Exon 8 of 8	NP_060901.2
	DOK5	NM_177959.3		c.*564G>A		3_prime_UTR	Exon 8 of 8	NP_808874.1	Q9P104-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOK5	ENST00000262593.10	TSL:1 MANE Select	c.*564G>A	3_prime_UTR	Exon 8 of 8	ENSP00000262593.5	Q9P104-1
DOK5	ENST00000939307.1		c.*564G>A	3_prime_UTR	Exon 8 of 8	ENSP00000609366.1
DOK5	ENST00000395939.5	TSL:1	c.*564G>A	downstream_gene	N/A	ENSP00000379270.1	Q9P104-2

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82698

AN:

151918

Hom.:

22710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.489

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.534

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

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:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.545

AC:

82809

AN:

152036

Hom.:

22754

Cov.:

AF XY:

0.541

AC XY:

40178

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.556

AC:

23054

AN:

41464

American (AMR)

AF:

0.587

AC:

8964

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1768

AN:

3470

East Asian (EAS)

AF:

0.389

AC:

2011

AN:

5168

South Asian (SAS)

AF:

0.502

AC:

2423

AN:

4826

European-Finnish (FIN)

AF:

0.489

AC:

5155

AN:

10550

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.554

AC:

37640

AN:

67960

Other (OTH)

AF:

0.535

AC:

1130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1929

3858

5787

7716

9645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.553

Hom.:

38302

Bravo

AF:

0.553

Asia WGS

AF:

0.459

AC:

1600

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.28

(source)

DANN

Benign

0.54

PhyloP100

-0.45

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over