11-822000-ATCCC-ATCCCTCCC
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_020376.4(PNPLA2):c.475_478dup(p.Gln160ProfsTer19) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000124 in 1,613,496 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PNPLA2
NM_020376.4 frameshift
NM_020376.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.10
Genes affected
PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-822000-A-ATCCC is Pathogenic according to our data. Variant chr11-822000-A-ATCCC is described in ClinVar as [Pathogenic]. Clinvar id is 65421.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| PNPLA2 | NM_020376.4 | c.475_478dup | p.Gln160ProfsTer19 | frameshift_variant | 4/10 | ENST00000336615.9 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PNPLA2 | ENST00000336615.9 | c.475_478dup | p.Gln160ProfsTer19 | frameshift_variant | 4/10 | 1 | NM_020376.4 | P1 | |
| PNPLA2 | ENST00000525250.5 | n.1081_1084dup | non_coding_transcript_exon_variant | 2/6 | 2 | ||||
| PNPLA2 | ENST00000534561.1 | n.142_145dup | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
| PNPLA2 | ENST00000531923.1 | upstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151966Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251314Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135874
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461530Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727046
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GnomAD4 genome 0.00000658 AC: 1AN: 151966Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74210
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Neutral lipid storage myopathy Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2007 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at