chr14-50911872-CT-C
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PVS1_ModerateBP6_Very_StrongBA1
The NM_002863.5(PYGL):c.1828-2del variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.46 ( 17685 hom., cov: 0)
Exomes 𝑓: 0.37 ( 107281 hom. )
Consequence
PYGL
NM_002863.5 splice_acceptor
NM_002863.5 splice_acceptor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
Genes affected
PYGL (HGNC:9725): (glycogen phosphorylase L) This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.05542453 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.4, offset of 0 (no position change), new splice context is: gtttgaccttcttccccaAGgct. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
BP6
Variant 14-50911872-CT-C is Benign according to our data. Variant chr14-50911872-CT-C is described in ClinVar as [Benign]. Clinvar id is 194627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-50911872-CT-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYGL | NM_002863.5 | c.1828-2del | splice_acceptor_variant | ENST00000216392.8 | |||
PYGL | NM_001163940.2 | c.1726-2del | splice_acceptor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGL | ENST00000216392.8 | c.1828-2del | splice_acceptor_variant | 1 | NM_002863.5 | P1 | |||
PYGL | ENST00000532462.5 | c.1828-2del | splice_acceptor_variant | 1 | |||||
PYGL | ENST00000544180.6 | c.1726-2del | splice_acceptor_variant | 2 | |||||
PYGL | ENST00000532107.2 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.460 AC: 69868AN: 151864Hom.: 17649 Cov.: 0
GnomAD3 genomes
AF:
AC:
69868
AN:
151864
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.441 AC: 110756AN: 251422Hom.: 26796 AF XY: 0.426 AC XY: 57930AN XY: 135878
GnomAD3 exomes
AF:
AC:
110756
AN:
251422
Hom.:
AF XY:
AC XY:
57930
AN XY:
135878
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.371 AC: 542589AN: 1461716Hom.: 107281 Cov.: 0 AF XY: 0.372 AC XY: 270277AN XY: 727164
GnomAD4 exome
AF:
AC:
542589
AN:
1461716
Hom.:
Cov.:
0
AF XY:
AC XY:
270277
AN XY:
727164
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.460 AC: 69959AN: 151982Hom.: 17685 Cov.: 0 AF XY: 0.464 AC XY: 34462AN XY: 74294
GnomAD4 genome
AF:
AC:
69959
AN:
151982
Hom.:
Cov.:
0
AF XY:
AC XY:
34462
AN XY:
74294
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1884
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 06, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 5552/12518=44.35% - |
Glycogen storage disease, type VI Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Benign:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 23, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at