rs376015031
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003560.4(PLA2G6):c.209+6T>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.000046 in 152,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PLA2G6
NM_003560.4 splice_donor_region, intron
NM_003560.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.8326
2
Clinical Significance
Conservation
PhyloP100: 5.41
Genes affected
PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLA2G6 | NM_003560.4 | c.209+6T>C | splice_donor_region_variant, intron_variant | ENST00000332509.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLA2G6 | ENST00000332509.8 | c.209+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_003560.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249580Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134994
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1453922Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 723702
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74294
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 20, 2016 | - - |
Infantile neuroaxonal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 12, 2021 | This sequence change falls in intron 2 of the PLA2G6 gene. It does not directly change the encoded amino acid sequence of the PLA2G6 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs376015031, ExAC 0.01%). This variant has not been reported in the literature in individuals with PLA2G6-related conditions. ClinVar contains an entry for this variant (Variation ID: 448040). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at