chr20-17436861-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002594.5(PCSK2):c.863C>T(p.Ala288Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002594.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK2 | NM_002594.5 | c.863C>T | p.Ala288Val | missense_variant | 8/12 | ENST00000262545.7 | |
PCSK2 | NM_001201528.2 | c.806C>T | p.Ala269Val | missense_variant | 9/13 | ||
PCSK2 | NM_001201529.3 | c.758C>T | p.Ala253Val | missense_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK2 | ENST00000262545.7 | c.863C>T | p.Ala288Val | missense_variant | 8/12 | 1 | NM_002594.5 | P1 | |
PCSK2 | ENST00000377899.5 | c.806C>T | p.Ala269Val | missense_variant | 9/13 | 1 | |||
PCSK2 | ENST00000536609.1 | c.758C>T | p.Ala253Val | missense_variant | 7/11 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459932Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726256
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | The c.863C>T (p.A288V) alteration is located in exon 8 (coding exon 8) of the PCSK2 gene. This alteration results from a C to T substitution at nucleotide position 863, causing the alanine (A) at amino acid position 288 to be replaced by a valine (V). 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
Publications
No publications associated with this variant yet.