20-54651088-T-C

Variant names:

• chr20-54651088-T-C
• rs15899
• NM_018431.5:c.*609T>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.*609T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,944 control chromosomes in the GnomAD database, including 16,696 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 0.44 (16696 hom., cov: 33)
  • Exomes 𝑓: 0.42 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOK5 NM_018431.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.537 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	NM_018431.5	MANE Select	c.*609T>C		3_prime_UTR	Exon 8 of 8	NP_060901.2
	DOK5	NM_177959.3		c.*609T>C		3_prime_UTR	Exon 8 of 8	NP_808874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.*609T>C		3_prime_UTR	Exon 8 of 8	ENSP00000262593.5
	DOK5	ENST00000395939.5	TSL:1	c.*609T>C		downstream_gene	N/A	ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67534 AN: 151824 Hom.: 16685 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.515

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.417 AC: 15 AN: 36 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 8 AN XY: 24

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 12 AN: 30

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00367175), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.445 AC: 67574 AN: 151944 Hom.: 16696 Cov.: 33 AF XY: 0.447 AC XY: 33178 AN XY: 74240

African (AFR) AF: 0.220 AC: 9113 AN: 41506

American (AMR) AF: 0.478 AC: 7299 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2468 AN: 3464

East Asian (EAS) AF: 0.447 AC: 2307 AN: 5158

South Asian (SAS) AF: 0.528 AC: 2537 AN: 4808

European-Finnish (FIN) AF: 0.502 AC: 5289 AN: 10544

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.542 AC: 36780 AN: 67886

Other (OTH) AF: 0.520 AC: 1091 AN: 2100

Alfa AF: 0.518 Hom.: 82640

Bravo AF: 0.434

Asia WGS AF: 0.498 AC: 1734 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.47
PhyloP100		-0.63
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: rs15899; hg19: chr20-53267627;