14-24094416-T-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting
The NM_001291556.2(PCK2):c.-226T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000641 in 1,559,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001291556.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCK2 | NM_004563.4 | c.11T>G | p.Leu4Trp | missense_variant | Exon 1 of 10 | ENST00000216780.9 | NP_004554.3 | |
NRL | NM_001354768.3 | c.-27-11541A>C | intron_variant | Intron 1 of 2 | ENST00000561028.6 | NP_001341697.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCK2 | ENST00000216780.9 | c.11T>G | p.Leu4Trp | missense_variant | Exon 1 of 10 | 1 | NM_004563.4 | ENSP00000216780.4 | ||
NRL | ENST00000561028.6 | c.-27-11541A>C | intron_variant | Intron 1 of 2 | 2 | NM_001354768.3 | ENSP00000454062.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000185 AC: 3AN: 162080Hom.: 0 AF XY: 0.0000224 AC XY: 2AN XY: 89324
GnomAD4 exome AF: 0.00000497 AC: 7AN: 1407506Hom.: 0 Cov.: 31 AF XY: 0.00000717 AC XY: 5AN XY: 697250
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with PCK2-related conditions. This variant is present in population databases (rs761260711, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 4 of the PCK2 protein (p.Leu4Trp). ClinVar contains an entry for this variant (Variation ID: 2165082). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at