chr20-17331428-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002594.5(PCSK2):​c.283-26899A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,008 control chromosomes in the GnomAD database, including 16,083 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 0.44 ( 16083 hom., cov: 32)

Consequence

PCSK2
NM_002594.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.996
Variant links:
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=-0.89).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCSK2NM_002594.5 linkuse as main transcriptc.283-26899A>T intron_variant ENST00000262545.7 NP_002585.2
PCSK2NM_001201528.2 linkuse as main transcriptc.226-26899A>T intron_variant NP_001188457.1
PCSK2NM_001201529.3 linkuse as main transcriptc.178-26899A>T intron_variant NP_001188458.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCSK2ENST00000262545.7 linkuse as main transcriptc.283-26899A>T intron_variant 1 NM_002594.5 ENSP00000262545 P1P16519-1
PCSK2ENST00000377899.5 linkuse as main transcriptc.226-26899A>T intron_variant 1 ENSP00000367131 P16519-3
PCSK2ENST00000536609.1 linkuse as main transcriptc.178-26899A>T intron_variant 2 ENSP00000437458 P16519-2
PCSK2ENST00000470007.1 linkuse as main transcriptn.278-26899A>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.437
AC:
66381
AN:
151890
Hom.:
16087
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.246
Gnomad AMI
AF:
0.801
Gnomad AMR
AF:
0.414
Gnomad ASJ
AF:
0.475
Gnomad EAS
AF:
0.224
Gnomad SAS
AF:
0.549
Gnomad FIN
AF:
0.522
Gnomad MID
AF:
0.500
Gnomad NFE
AF:
0.546
Gnomad OTH
AF:
0.459
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.437
AC:
66389
AN:
152008
Hom.:
16083
Cov.:
32
AF XY:
0.437
AC XY:
32474
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.245
Gnomad4 AMR
AF:
0.415
Gnomad4 ASJ
AF:
0.475
Gnomad4 EAS
AF:
0.224
Gnomad4 SAS
AF:
0.548
Gnomad4 FIN
AF:
0.522
Gnomad4 NFE
AF:
0.546
Gnomad4 OTH
AF:
0.456
Alfa
AF:
0.479
Hom.:
2268
Bravo
AF:
0.420
Asia WGS
AF:
0.389
AC:
1354
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
6.7
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs727472; hg19: chr20-17312073; API