chr18-69698432-A-T

Variant names:

• chr18-69698432-A-T
• rs4426448
• NM_152721.6:c.438A>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152721.6(DOK6):​c.438A>T​(p.Thr146Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.795 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK6	NM_152721.6	c.438A>T	p.Thr146Thr	synonymous_variant	Exon 5 of 8	ENST00000382713.10	NP_689934.2
DOK6	XM_017025610.2	c.114A>T	p.Thr38Thr	synonymous_variant	Exon 3 of 6		XP_016881099.1
DOK6	XM_017025611.2	c.114A>T	p.Thr38Thr	synonymous_variant	Exon 3 of 6		XP_016881100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.438A>T	p.Thr146Thr	synonymous_variant	Exon 5 of 8	1	NM_152721.6	ENSP00000372160.5
DOK6	ENST00000582992.1	c.147A>T	p.Thr49Thr	synonymous_variant	Exon 2 of 3	3		ENSP00000462984.1
DOK6	ENST00000582172.5	n.409A>T		non_coding_transcript_exon_variant	Exon 4 of 4	3
DOK6	ENST00000584435.1	n.252A>T		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.53
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;