rs2840

chr20-54651037-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.*558G>A		3_prime_UTR_variant	8/8	ENST00000262593.10
DOK5	NM_177959.3	c.*558G>A		3_prime_UTR_variant	8/8
DOK5	XM_011528904.2	c.*558G>A		3_prime_UTR_variant	8/8
DOK5	XM_024451946.2	c.*558G>A		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.*558G>A		3_prime_UTR_variant	8/8	1	NM_018431.5	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31701 AN: 152012 Hom.: 3527 Cov.: 33

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: 10 AN: 62 Hom.: 1 Cov.: 0 AF XY: 0.167 AC XY: 5 AN XY: 30

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.209 AC: 31742 AN: 152130 Hom.: 3539 Cov.: 33 AF XY: 0.204 AC XY: 15176 AN XY: 74386

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.207

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
Dann	Benign	0.58

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: rs2840; hg19: chr20-53267576;