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
• Publications: 4 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018431.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	NM_018431.5	MANE Select	c.600-146C>T		intron	N/A	NP_060901.2
	DOK5	NM_177959.3		c.276-146C>T		intron	N/A	NP_808874.1	Q9P104-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.600-146C>T		intron	N/A	ENSP00000262593.5	Q9P104-1
	DOK5	ENST00000395939.5	TSL:1	c.276-146C>T		intron	N/A	ENSP00000379270.1	Q9P104-2
	DOK5	ENST00000939307.1		c.561-146C>T		intron	N/A	ENSP00000609366.1

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

African (AFR) AF: 0.877 AC: 14097 AN: 16080

American (AMR) AF: 0.463 AC: 4322 AN: 9332

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 4027 AN: 12426

East Asian (EAS) AF: 0.00103 AC: 27 AN: 26278

South Asian (SAS) AF: 0.144 AC: 2315 AN: 16046

European-Finnish (FIN) AF: 0.251 AC: 6224 AN: 24800

Middle Eastern (MID) AF: 0.314 AC: 709 AN: 2260

European-Non Finnish (NFE) AF: 0.345 AC: 190867 AN: 552624

Other (OTH) 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

African (AFR) AF: 0.852 AC: 35381 AN: 41548

American (AMR) AF: 0.448 AC: 6856 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5182

South Asian (SAS) AF: 0.132 AC: 637 AN: 4832

European-Finnish (FIN) AF: 0.237 AC: 2506 AN: 10596

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23224 AN: 67992

Other (OTH) AF: 0.445 AC: 939 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.41
PhyloP100		0.026
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

Other links and lift over

dbSNP: rs6068915; hg19: chr20-53226781;