chr20-54650572-C-G

Position:

• chr20-54650572-C-G

Variant summary

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

The NM_018431.5(DOK5):​c.*93C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0467 in 1,227,530 control chromosomes in the GnomAD database, including 4,862 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 0.12 (2689 hom., cov: 33)
  • Exomes 𝑓: 0.036 (2173 hom.)
• Consequence: DOK5 NM_018431.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.*93C>G		3_prime_UTR_variant	8/8	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.*93C>G		3_prime_UTR_variant	8/8		NP_808874.1
DOK5	XM_024451946.2	c.*93C>G		3_prime_UTR_variant	8/8		XP_024307714.1
DOK5	XM_011528904.2	c.*93C>G		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.*93C>G		3_prime_UTR_variant	8/8	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.*93C>G		3_prime_UTR_variant	8/8	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18318 AN: 152092 Hom.: 2685 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0251

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0362 AC: 38958 AN: 1075320 Hom.: 2173 Cov.: 14 AF XY: 0.0344 AC XY: 18804 AN XY: 546048

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.0421

Gnomad4 ASJ exome AF: 0.0261

Gnomad4 EAS exome AF: 0.000109

Gnomad4 SAS exome AF: 0.0171

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.0301

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.120 AC: 18341 AN: 152210 Hom.: 2689 Cov.: 33 AF XY: 0.116 AC XY: 8667 AN XY: 74436

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.0587

Gnomad4 ASJ AF: 0.0251

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0795 Hom.: 192

Bravo AF: 0.135

Asia WGS AF: 0.0280 AC: 96 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	0.39
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2023454; hg19: chr20-53267111;