20-54616992-T-G

Position:

• chr20-54616992-T-G

Variant summary

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

The NM_018431.5(DOK5):​c.735+6469T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,732 control chromosomes in the GnomAD database, including 21,471 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 0.47 (21471 hom., cov: 30)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.27

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.735+6469T>G		intron_variant		ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.411+6469T>G		intron_variant			NP_808874.1
DOK5	XM_024451946.2	c.699+6469T>G		intron_variant			XP_024307714.1
DOK5	XM_011528904.2	c.411+6469T>G		intron_variant			XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.735+6469T>G		intron_variant		1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.411+6469T>G		intron_variant		1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70539 AN: 151616 Hom.: 21405 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.00503

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.466 AC: 70677 AN: 151732 Hom.: 21471 Cov.: 30 AF XY: 0.452 AC XY: 33517 AN XY: 74138

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.00484

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.442

Alfa AF: 0.202 Hom.: 359

Bravo AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.29

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: rs6068916; hg19: chr20-53233531;