rs10513968

Positions:

• chr18-69615905-A-G

Variant summary

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

The NM_152721.6(DOK6):​c.289+16407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,002 control chromosomes in the GnomAD database, including 25,522 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 0.58 (25522 hom., cov: 32)
• Consequence: DOK6 NM_152721.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK6	NM_152721.6	c.289+16407A>G		intron_variant		ENST00000382713.10	NP_689934.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.289+16407A>G		intron_variant		1	NM_152721.6	ENSP00000372160	P1
	ENST00000583991.1	n.151+2639T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87470 AN: 151884 Hom.: 25507 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.576 AC: 87531 AN: 152002 Hom.: 25522 Cov.: 32 AF XY: 0.578 AC XY: 42951 AN XY: 74320

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.570

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.560

Alfa AF: 0.614 Hom.: 14166

Bravo AF: 0.569

Asia WGS AF: 0.605 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.62

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: rs10513968; hg19: chr18-67283141;