14-24096935-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001308054.2(PCK2):c.-330C>T 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 0.0000205 in 1,613,414 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_001308054.2 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCK2 | NM_004563.4 | c.73C>T | p.Arg25Cys | missense_variant | Exon 2 of 10 | ENST00000216780.9 | NP_004554.3 | |
NRL | NM_001354768.3 | c.-27-14060G>A | 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.73C>T | p.Arg25Cys | missense_variant | Exon 2 of 10 | 1 | NM_004563.4 | ENSP00000216780.4 | ||
NRL | ENST00000561028.6 | c.-27-14060G>A | intron_variant | Intron 1 of 2 | 2 | NM_001354768.3 | ENSP00000454062.2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251004Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135688
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461284Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 726972
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152130Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.73C>T (p.R25C) alteration is located in exon 2 (coding exon 2) of the PCK2 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the arginine (R) at amino acid position 25 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 25 of the PCK2 protein (p.Arg25Cys). This variant is present in population databases (rs769558514, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with PCK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 3210243). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at