rs6023367

Positions:

• chr20-54575372-G-A

Variant summary

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

The ENST00000262593.10(DOK5):​c.175-13111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,082 control chromosomes in the GnomAD database, including 14,800 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 0.35 (14800 hom., cov: 32)
• Consequence: DOK5 ENST00000262593.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.175-13111G>A		intron_variant		ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-150-13111G>A		intron_variant			NP_808874.1
DOK5	XM_011528904.2	c.-150-13111G>A		intron_variant			XP_011527206.1
DOK5	XM_024451946.2	c.139-13111G>A		intron_variant			XP_024307714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.175-13111G>A		intron_variant		1	NM_018431.5	ENSP00000262593	P1
DOK5	ENST00000395939.5	c.-150-13111G>A		intron_variant		1		ENSP00000379270

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53202 AN: 151964 Hom.: 14744 Cov.: 32

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.351 AC: 53323 AN: 152082 Hom.: 14800 Cov.: 32 AF XY: 0.339 AC XY: 25205 AN XY: 74374

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.304

Alfa AF: 0.228 Hom.: 6721

Bravo AF: 0.373

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.19

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: rs6023367; hg19: chr20-53191911;