rs10513968

Variant names:

• chr18-69615905-A-G
• rs10513968
• NM_152721.6:c.289+16407A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000265643 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DOK6	NM_152721.6	c.289+16407A>G		intron_variant	Intron 3 of 7	ENST00000382713.10	NP_689934.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.289+16407A>G		intron_variant	Intron 3 of 7	1	NM_152721.6	ENSP00000372160.5
ENSG00000265643	ENST00000583991.1	n.151+2639T>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.477 AC: 19769 AN: 41424

American (AMR) AF: 0.613 AC: 9369 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2945 AN: 5170

South Asian (SAS) AF: 0.674 AC: 3248 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6473 AN: 10568

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42081 AN: 67958

Other (OTH) AF: 0.560 AC: 1183 AN: 2112

Alfa AF: 0.612 Hom.: 15672

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
PhyloP100		0.97
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: rs10513968; hg19: chr18-67283141;