X-30668120-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001205019.2(GK):c.259+2T>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001205019.2 splice_donor, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 803746Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0AN XY: 222024
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
not provided Pathogenic:1
The c.259+2 T>C splice site variant in the GK gene destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this variant has not been previously reported to our knowledge, we interpret it as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at