rs17184557

chr18-69475621-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152721.6(DOK6):c.66+74311T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,166 control chromosomes in the GnomAD database, including 3,122 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 0.19 (3122 hom., cov: 32)
• Consequence: DOK6 NM_152721.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK6	NM_152721.6	c.66+74311T>A		intron_variant		ENST00000382713.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK6	ENST00000382713.10	c.66+74311T>A		intron_variant		1	NM_152721.6	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28173 AN: 152048 Hom.: 3123 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28187 AN: 152166 Hom.: 3122 Cov.: 32 AF XY: 0.189 AC XY: 14080 AN XY: 74364

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.166

Alfa AF: 0.208 Hom.: 1982

Bravo AF: 0.174

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.4
Dann	Benign	0.47

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: rs17184557; hg19: chr18-67142857;