rs797045889
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_003560.4(PLA2G6):c.945_947dupCGC(p.Ala316dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000567 in 1,412,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
PLA2G6
NM_003560.4 disruptive_inframe_insertion
NM_003560.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.59
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_003560.4. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 22-38132960-C-CGCG is Pathogenic according to our data. Variant chr22-38132960-C-CGCG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211911.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLA2G6 | NM_003560.4 | c.945_947dupCGC | p.Ala316dup | disruptive_inframe_insertion | 7/17 | ENST00000332509.8 | NP_003551.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLA2G6 | ENST00000332509.8 | c.945_947dupCGC | p.Ala316dup | disruptive_inframe_insertion | 7/17 | 1 | NM_003560.4 | ENSP00000333142.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000567 AC: 8AN: 1412064Hom.: 0 Cov.: 31 AF XY: 0.00000716 AC XY: 5AN XY: 697918
GnomAD4 exome
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1412064
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31
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5
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697918
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Neurodegeneration with brain iron accumulation 2B Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 20, 2021 | Variant summary: PLA2G6 c.945_947dupCGC (p.Ala316dup) results in an in-frame duplication that is predicted to duplicate one amino acid into the encoded protein. The variant was absent in 174588 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.945_947dupCGC has been reported in the literature in an individual affected with Neurodegeneration With Brain Iron Accumulation in the compound heterozygous state (Al-Maawali_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at