20-54568983-CAAAAAAA-CAAAA

Position:

• chr20-54568983-CAAAAAAA-CAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018431.5(DOK5):​c.174+13963_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 0.011 (15 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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1087/96172) while in subpopulation AFR AF= 0.0372 (1001/26932). AF 95% confidence interval is 0.0353. There are 15 homozygotes in gnomad4. There are 494 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13963_174+13965del		intron_variant		ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13963_-151+13965del		intron_variant			NP_808874.1
DOK5	XM_011528904.2	c.-151+13963_-151+13965del		intron_variant			XP_011527206.1
DOK5	XM_024451946.2	c.138+13963_138+13965del		intron_variant			XP_024307714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.174+13963_174+13965del		intron_variant		1	NM_018431.5	ENSP00000262593	P1
DOK5	ENST00000395939.5	c.-151+13963_-151+13965del		intron_variant		1		ENSP00000379270

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1086 AN: 96208 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00470

Gnomad ASJ AF: 0.000403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00145

Gnomad MID AF: 0.00510

Gnomad NFE AF: 0.000516

Gnomad OTH AF: 0.0103

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

GnomAD4 genome AF: 0.0113 AC: 1087 AN: 96172 Hom.: 15 Cov.: 0 AF XY: 0.0110 AC XY: 494 AN XY: 44766

Gnomad4 AFR AF: 0.0372

Gnomad4 AMR AF: 0.00470

Gnomad4 ASJ AF: 0.000403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00145

Gnomad4 NFE AF: 0.000516

Gnomad4 OTH AF: 0.0103

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;