chr20-54556389-A-C

Position:

• chr20-54556389-A-C

Variant summary

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

The NM_018431.5(DOK5):​c.174+1349A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,152 control chromosomes in the GnomAD database, including 6,182 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 0.23 (6182 hom., cov: 32)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+1349A>C		intron_variant		ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+1349A>C		intron_variant			NP_808874.1
DOK5	XM_011528904.2	c.-151+1349A>C		intron_variant			XP_011527206.1
DOK5	XM_024451946.2	c.138+1349A>C		intron_variant			XP_024307714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.174+1349A>C		intron_variant		1	NM_018431.5	ENSP00000262593	P1
DOK5	ENST00000395939.5	c.-151+1349A>C		intron_variant		1		ENSP00000379270

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35304 AN: 152034 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.233 AC: 35395 AN: 152152 Hom.: 6182 Cov.: 32 AF XY: 0.228 AC XY: 16978 AN XY: 74398

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.204

Alfa AF: 0.190 Hom.: 631

Bravo AF: 0.253

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.61

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: rs6023357; hg19: chr20-53172928;