rs2842

Positions:

• chr20-54651043-G-A
• chr20-54651043-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.*564G>A		3_prime_UTR_variant	8/8	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.*564G>A		3_prime_UTR_variant	8/8		NP_808874.1
DOK5	XM_024451946.2	c.*564G>A		3_prime_UTR_variant	8/8		XP_024307714.1
DOK5	XM_011528904.2	c.*564G>A		3_prime_UTR_variant	8/8		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.*564G>A		3_prime_UTR_variant	8/8	1	NM_018431.5	ENSP00000262593.5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82698 AN: 151918 Hom.: 22710 Cov.: 33

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: 33 AN: 66 Hom.: 9 Cov.: 0 AF XY: 0.500 AC XY: 18 AN XY: 36

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.545 AC: 82809 AN: 152036 Hom.: 22754 Cov.: 33 AF XY: 0.541 AC XY: 40178 AN XY: 74300

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.535

Alfa AF: 0.551 Hom.: 29827

Bravo AF: 0.553

Asia WGS AF: 0.459 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.54

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: rs2842; hg19: chr20-53267582;