chr18-69739102-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_152721.6(DOK6):c.737G>A(p.Arg246Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000328 in 1,613,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_152721.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOK6 | NM_152721.6 | c.737G>A | p.Arg246Gln | missense_variant, splice_region_variant | 6/8 | ENST00000382713.10 | |
DOK6 | XM_017025610.2 | c.413G>A | p.Arg138Gln | missense_variant, splice_region_variant | 4/6 | ||
DOK6 | XM_017025611.2 | c.413G>A | p.Arg138Gln | missense_variant, splice_region_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOK6 | ENST00000382713.10 | c.737G>A | p.Arg246Gln | missense_variant, splice_region_variant | 6/8 | 1 | NM_152721.6 | P1 | |
DOK6 | ENST00000582992.1 | c.449G>A | p.Arg150Gln | missense_variant | 3/3 | 3 | |||
DOK6 | ENST00000577609.1 | n.118G>A | splice_region_variant, non_coding_transcript_exon_variant | 1/4 | 3 | ||||
DOK6 | ENST00000584435.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 250892Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135598
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461464Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727060
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | The c.737G>A (p.R246Q) alteration is located in exon 6 (coding exon 6) of the DOK6 gene. This alteration results from a G to A substitution at nucleotide position 737, causing the arginine (R) at amino acid position 246 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at