20-54610242-C-T

Variant names:

• chr20-54610242-C-T
• rs6068915
• NM_018431.5:c.600-146C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018431.5(DOK5):​c.600-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 843,342 control chromosomes in the GnomAD database, including 66,012 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 (21561 hom., cov: 34)
  • Exomes 𝑓: 0.34 (44451 hom.)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.600-146C>T		intron_variant	Intron 5 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.276-146C>T		intron_variant	Intron 5 of 7		NP_808874.1
DOK5	XM_024451946.2	c.564-146C>T		intron_variant	Intron 5 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.276-146C>T		intron_variant	Intron 5 of 7		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.600-146C>T		intron_variant	Intron 5 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.276-146C>T		intron_variant	Intron 5 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70899 AN: 152120 Hom.: 21499 Cov.: 34

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.338 AC: 233371 AN: 691104 Hom.: 44451 AF XY: 0.335 AC XY: 113582 AN XY: 338580

Gnomad4 AFR exome AF: 0.877 AC: 14097 AN: 16080

Gnomad4 AMR exome AF: 0.463 AC: 4322 AN: 9332

Gnomad4 ASJ exome AF: 0.324 AC: 4027 AN: 12426

Gnomad4 EAS exome AF: 0.00103 AC: 27 AN: 26278

Gnomad4 SAS exome AF: 0.144 AC: 2315 AN: 16046

Gnomad4 FIN exome AF: 0.251 AC: 6224 AN: 24800

Gnomad4 NFE exome AF: 0.345 AC: 190867 AN: 552624

Gnomad4 Remaining exome AF: 0.345 AC: 10783 AN: 31258

GnomAD4 genome AF: 0.467 AC: 71040 AN: 152238 Hom.: 21561 Cov.: 34 AF XY: 0.453 AC XY: 33717 AN XY: 74440

Gnomad4 AFR AF: 0.852 AC: 0.851569 AN: 0.851569

Gnomad4 AMR AF: 0.448 AC: 0.448046 AN: 0.448046

Gnomad4 ASJ AF: 0.328 AC: 0.327666 AN: 0.327666

Gnomad4 EAS AF: 0.00521 AC: 0.00521034 AN: 0.00521034

Gnomad4 SAS AF: 0.132 AC: 0.131829 AN: 0.131829

Gnomad4 FIN AF: 0.237 AC: 0.236504 AN: 0.236504

Gnomad4 NFE AF: 0.342 AC: 0.34157 AN: 0.34157

Gnomad4 OTH AF: 0.445 AC: 0.445024 AN: 0.445024

Alfa AF: 0.422 Hom.: 2052

Bravo AF: 0.504

Asia WGS AF: 0.136 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.41
Mutation Taster		=100/0	polymorphism (auto)

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: rs6068915; hg19: chr20-53226781;