rs6080699
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002594.5(PCSK2):c.886-101G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,286,676 control chromosomes in the GnomAD database, including 78,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.26 ( 6489 hom., cov: 33)
Exomes 𝑓: 0.35 ( 72300 hom. )
Consequence
PCSK2
NM_002594.5 intron
NM_002594.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.977
Genes affected
PCSK2 (HGNC:8744): (proprotein convertase subtilisin/kexin type 2) This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The protein undergoes an initial autocatalytic processing event and interacts with a neuroendocrine secretory protein in the ER, exits the ER and sorts to secretory granules, where it is cleaved and catalytically activated during intracellular transport. The encoded protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Single nucleotide polymorphisms in this gene may increase susceptibility to myocardial infarction and type 2 diabetes. This gene may also play a role in tumor development and progression. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCSK2 | NM_002594.5 | c.886-101G>C | intron_variant | ENST00000262545.7 | |||
PCSK2 | NM_001201528.2 | c.829-101G>C | intron_variant | ||||
PCSK2 | NM_001201529.3 | c.781-101G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCSK2 | ENST00000262545.7 | c.886-101G>C | intron_variant | 1 | NM_002594.5 | P1 | |||
PCSK2 | ENST00000377899.5 | c.829-101G>C | intron_variant | 1 | |||||
PCSK2 | ENST00000536609.1 | c.781-101G>C | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.261 AC: 39694AN: 152038Hom.: 6492 Cov.: 33
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GnomAD4 exome AF: 0.349 AC: 395657AN: 1134520Hom.: 72300 AF XY: 0.354 AC XY: 201718AN XY: 569658
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GnomAD4 genome ? AF: 0.261 AC: 39678AN: 152156Hom.: 6489 Cov.: 33 AF XY: 0.264 AC XY: 19674AN XY: 74382
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at