20-54568983-CAAAAAAA-CAAAAAAAA

Variant summary

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

The NM_018431.5(DOK5):c.174+13965dup 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 0.040 (193 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 = 0.119 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 3831 AN: 96148 Hom.: 193 Cov.: 0

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00323

Gnomad EAS AF: 0.00420

Gnomad SAS AF: 0.00356

Gnomad FIN AF: 0.000870

Gnomad MID AF: 0.0153

Gnomad NFE AF: 0.00658

Gnomad OTH AF: 0.0310

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

GnomAD4 genome AF: 0.0399 AC: 3838 AN: 96112 Hom.: 193 Cov.: 0 AF XY: 0.0387 AC XY: 1731 AN XY: 44744

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.00323

Gnomad4 EAS AF: 0.00422

Gnomad4 SAS AF: 0.00359

Gnomad4 FIN AF: 0.000870

Gnomad4 NFE AF: 0.00658

Gnomad4 OTH AF: 0.0309

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;