20-54568983-CAAAAAAA-CAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018431.5(DOK5):c.174+13964_174+13965del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (77 hom., cov: 0)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.174+13964_174+13965del		intron_variant		ENST00000262593.10
DOK5	NM_177959.3	c.-151+13964_-151+13965del		intron_variant
DOK5	XM_011528904.2	c.-151+13964_-151+13965del		intron_variant
DOK5	XM_024451946.2	c.138+13964_138+13965del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.174+13964_174+13965del		intron_variant		1	NM_018431.5	P1
DOK5	ENST00000395939.5	c.-151+13964_-151+13965del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 3381 AN: 96270 Hom.: 77 Cov.: 0

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00169

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.00754

Gnomad MID AF: 0.0153

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0293

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

GnomAD4 genome AF: 0.0352 AC: 3391 AN: 96234 Hom.: 77 Cov.: 0 AF XY: 0.0348 AC XY: 1559 AN XY: 44790

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.00754

Gnomad4 NFE AF: 0.0212

Gnomad4 OTH AF: 0.0300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs10542523; hg19: chr20-53185522;