rs4426448

Positions:

• chr18-69698432-A-G
• chr18-69698432-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152721.6(DOK6):​c.438A>G​(p.Thr146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,612,720 control chromosomes in the GnomAD database, including 176,726 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 0.46 (16419 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160307 hom.)
• Consequence: DOK6 NM_152721.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795

Genes affected

DOK6 (HGNC:28301): (docking protein 6) DOK6 is a member of the DOK (see DOK1; MIM 602919) family of intracellular adaptors that play a role in the RET (MIM 164761) signaling cascade (Crowder et al., 2004 [PubMed 15286081]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.795 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK6	NM_152721.6	c.438A>G	p.Thr146=	synonymous_variant	5/8	ENST00000382713.10	NP_689934.2
DOK6	XM_017025610.2	c.114A>G	p.Thr38=	synonymous_variant	3/6		XP_016881099.1
DOK6	XM_017025611.2	c.114A>G	p.Thr38=	synonymous_variant	3/6		XP_016881100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.438A>G	p.Thr146=	synonymous_variant	5/8	1	NM_152721.6	ENSP00000372160	P1
DOK6	ENST00000582992.1	c.150A>G	p.Thr50=	synonymous_variant	2/3	3		ENSP00000462984
DOK6	ENST00000582172.5	n.409A>G		non_coding_transcript_exon_variant	4/4	3
DOK6	ENST00000584435.1	n.252A>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69844 AN: 151964 Hom.: 16415 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.452

GnomAD3 exomes AF: 0.464 AC: 116000 AN: 250210 Hom.: 28065 AF XY: 0.463 AC XY: 62659 AN XY: 135250

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.369

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.754

Gnomad SAS exome AF: 0.421

Gnomad FIN exome AF: 0.499

Gnomad NFE exome AF: 0.462

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.466 AC: 680077 AN: 1460638 Hom.: 160307 Cov.: 42 AF XY: 0.464 AC XY: 337254 AN XY: 726648

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.378

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.672

Gnomad4 SAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.459 AC: 69878 AN: 152082 Hom.: 16419 Cov.: 32 AF XY: 0.459 AC XY: 34130 AN XY: 74342

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.448

Alfa AF: 0.456 Hom.: 19447

Bravo AF: 0.453

Asia WGS AF: 0.538 AC: 1873 AN: 3478

EpiCase AF: 0.454

EpiControl AF: 0.460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs4426448; hg19: chr18-67365668;