chr20-54643425-G-C

Variant names:

• chr20-54643425-G-C
• rs6064099
• NM_018431.5:c.736-33G>C

Variant summary

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

The NM_018431.5(DOK5):​c.736-33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,609,122 control chromosomes in the GnomAD database, including 71,834 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 0.36 (10762 hom., cov: 33)
  • Exomes 𝑓: 0.28 (61072 hom.)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.736-33G>C		intron_variant	Intron 6 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.412-33G>C		intron_variant	Intron 6 of 7		NP_808874.1
DOK5	XM_024451946.2	c.700-33G>C		intron_variant	Intron 6 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.412-33G>C		intron_variant	Intron 6 of 7		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.736-33G>C		intron_variant	Intron 6 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.412-33G>C		intron_variant	Intron 6 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54046 AN: 151990 Hom.: 10758 Cov.: 33

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.298 AC: 73453 AN: 246446 AF XY: 0.292

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.284 AC: 413408 AN: 1457014 Hom.: 61072 Cov.: 34 AF XY: 0.281 AC XY: 203289 AN XY: 724560

African (AFR) AF: 0.559 AC: 18692 AN: 33450

American (AMR) AF: 0.246 AC: 10971 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 6149 AN: 26000

East Asian (EAS) AF: 0.448 AC: 17756 AN: 39658

South Asian (SAS) AF: 0.240 AC: 20607 AN: 85996

European-Finnish (FIN) AF: 0.306 AC: 15589 AN: 50956

Middle Eastern (MID) AF: 0.228 AC: 1310 AN: 5756

European-Non Finnish (NFE) AF: 0.275 AC: 305067 AN: 1110334

Other (OTH) AF: 0.287 AC: 17267 AN: 60268

GnomAD4 genome AF: 0.356 AC: 54077 AN: 152108 Hom.: 10762 Cov.: 33 AF XY: 0.354 AC XY: 26345 AN XY: 74348

African (AFR) AF: 0.548 AC: 22748 AN: 41496

American (AMR) AF: 0.267 AC: 4079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2340 AN: 5170

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3281 AN: 10572

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18581 AN: 67980

Other (OTH) AF: 0.324 AC: 684 AN: 2112

Alfa AF: 0.301 Hom.: 1402

Bravo AF: 0.364

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.71
DANN	Benign	0.41
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6064099; hg19: chr20-53259964; COSMIC: COSV52821487;