20-54532944-C-T

Variant summary

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

The NM_018431.5(DOK5):c.67-21989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,230 control chromosomes in the GnomAD database, including 4,723 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 0.17 (4723 hom., cov: 33)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.67-21989C>T		intron_variant		ENST00000262593.10
DOK5	NM_177959.3	c.-258-21989C>T		intron_variant
DOK5	XM_011528904.2	c.-258-21989C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.67-21989C>T		intron_variant		1	NM_018431.5	P1
DOK5	ENST00000395939.5	c.-258-21989C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25581 AN: 152112 Hom.: 4694 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.142

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25669 AN: 152230 Hom.: 4723 Cov.: 33 AF XY: 0.164 AC XY: 12229 AN XY: 74446

Gnomad4 AFR AF: 0.466

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.0988

Gnomad4 SAS AF: 0.0780

Gnomad4 FIN AF: 0.0362

Gnomad4 NFE AF: 0.0374

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0669 Hom.: 1053

Bravo AF: 0.191

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.4
Dann	Benign	0.72

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: rs2426531; hg19: chr20-53149483;