rs6023376

Positions:

• chr20-54579175-G-C

Variant summary

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

The NM_018431.5(DOK5):​c.175-9308G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,934 control chromosomes in the GnomAD database, including 17,095 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 0.37 (17095 hom., cov: 32)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.175-9308G>C		intron_variant		ENST00000262593.10
DOK5	NM_177959.3	c.-150-9308G>C		intron_variant
DOK5	XM_011528904.2	c.-150-9308G>C		intron_variant
DOK5	XM_024451946.2	c.139-9308G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.175-9308G>C		intron_variant		1	NM_018431.5	P1
DOK5	ENST00000395939.5	c.-150-9308G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55589 AN: 151818 Hom.: 17035 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.367 AC: 55706 AN: 151934 Hom.: 17095 Cov.: 32 AF XY: 0.354 AC XY: 26253 AN XY: 74230

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0661

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.339

Alfa AF: 0.305 Hom.: 1411

Bravo AF: 0.396

Asia WGS AF: 0.0960 AC: 336 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.64

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: rs6023376; hg19: chr20-53195714;