rs15899

chr20-54651088-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018431.5(DOK5):c.*609T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,944 control chromosomes in the GnomAD database, including 16,696 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 0.44 (16696 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOK5 NM_018431.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.*609T>C		3_prime_UTR_variant	8/8	ENST00000262593.10
DOK5	NM_177959.3	c.*609T>C		3_prime_UTR_variant	8/8
DOK5	XM_011528904.2	c.*609T>C		3_prime_UTR_variant	8/8
DOK5	XM_024451946.2	c.*609T>C		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.*609T>C		3_prime_UTR_variant	8/8	1	NM_018431.5	P1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67534 AN: 151824 Hom.: 16685 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.515

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.417 AC: 15 AN: 36 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 8 AN XY: 24

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.400

GnomAD4 genome AF: 0.445 AC: 67574 AN: 151944 Hom.: 16696 Cov.: 33 AF XY: 0.447 AC XY: 33178 AN XY: 74240

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.520

Alfa AF: 0.540 Hom.: 37921

Bravo AF: 0.434

Asia WGS AF: 0.498 AC: 1734 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.93
Dann	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs15899; hg19: chr20-53267627;