ENST00000300730.10:c.139+55C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000300730.10(PGAP2):c.139+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,530,392 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 124 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 93 hom. )
Consequence
PGAP2
ENST00000300730.10 intron
ENST00000300730.10 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.434
Genes affected
PGAP2 (HGNC:17893): (post-GPI attachment to proteins 2) The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]
NUP98 (HGNC:8068): (nucleoporin 98 and 96 precursor) Nuclear pore complexes (NPCs) regulate the transport of macromolecules between the nucleus and cytoplasm, and are composed of many polypeptide subunits, many of which belong to the nucleoporin family. This gene belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to generate a 98 kDa nucleoporin and 96 kDa nucleoporin. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly (GLGF) repeat domain and participates in many cellular processes, including nuclear import, nuclear export, mitotic progression, and regulation of gene expression. The 96 kDa nucleoporin is a scaffold component of the NPC. Proteolytic cleavage is important for targeting of the proteins to the NPC. Translocations between this gene and many other partner genes have been observed in different leukemias. Rearrangements typically result in chimeras with the N-terminal GLGF domain of this gene to the C-terminus of the partner gene. Alternative splicing results in multiple transcript variants encoding different isoforms, at least two of which are proteolytically processed. Some variants lack the region that encodes the 96 kDa nucleoporin. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 11-3798037-C-T is Benign according to our data. Variant chr11-3798037-C-T is described in ClinVar as [Benign]. Clinvar id is 1235044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PGAP2 | NM_001346397.2 | c.58C>T | p.Pro20Ser | missense_variant | Exon 1 of 7 | NP_001333326.1 | ||
PGAP2 | XM_011520004.3 | c.58C>T | p.Pro20Ser | missense_variant | Exon 1 of 8 | XP_011518306.2 | ||
PGAP2 | XM_047426788.1 | c.58C>T | p.Pro20Ser | missense_variant | Exon 1 of 7 | XP_047282744.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PGAP2 | ENST00000300730.10 | c.139+55C>T | intron_variant | Intron 1 of 6 | 1 | ENSP00000300730.6 | ||||
PGAP2 | ENST00000396993.8 | c.-326+55C>T | intron_variant | Intron 1 of 5 | 1 | ENSP00000380190.6 | ||||
PGAP2 | ENST00000465237.6 | n.75+55C>T | intron_variant | Intron 1 of 2 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0220 AC: 3349AN: 152184Hom.: 123 Cov.: 33
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GnomAD4 exome AF: 0.00214 AC: 2951AN: 1378090Hom.: 93 Cov.: 31 AF XY: 0.00190 AC XY: 1291AN XY: 680094
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GnomAD4 genome AF: 0.0221 AC: 3371AN: 152302Hom.: 124 Cov.: 33 AF XY: 0.0217 AC XY: 1616AN XY: 74502
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
May 26, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at