2-11782200-GTCT-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PP3_ModerateBP3BP6_Very_StrongBS1BS2
The NM_001349206.2(LPIN1):c.964_966del(p.Ser322del) variant causes a inframe deletion, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,014 control chromosomes in the GnomAD database, including 44 homozygotes. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 24 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 20 hom. )
Consequence
LPIN1
NM_001349206.2 inframe_deletion, splice_region
NM_001349206.2 inframe_deletion, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.10
Genes affected
LPIN1 (HGNC:13345): (lipin 1) This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP3
?
Nonframeshift variant in repetitive region in NM_001349206.2
BP6
?
Variant 2-11782200-GTCT-G is Benign according to our data. Variant chr2-11782200-GTCT-G is described in ClinVar as [Likely_benign]. Clinvar id is 262597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1556/152188) while in subpopulation AFR AF= 0.0352 (1462/41502). AF 95% confidence interval is 0.0337. There are 24 homozygotes in gnomad4. There are 728 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 24 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LPIN1 | NM_001349206.2 | c.964_966del | p.Ser322del | inframe_deletion, splice_region_variant | 8/21 | ENST00000674199.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LPIN1 | ENST00000674199.1 | c.964_966del | p.Ser322del | inframe_deletion, splice_region_variant | 8/21 | NM_001349206.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0102 AC: 1554AN: 152070Hom.: 24 Cov.: 32
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GnomAD3 exomes AF: 0.00238 AC: 595AN: 250492Hom.: 5 AF XY: 0.00181 AC XY: 246AN XY: 135590
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GnomAD4 exome AF: 0.00103 AC: 1504AN: 1460826Hom.: 20 AF XY: 0.000890 AC XY: 647AN XY: 726800
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2018 | This variant is associated with the following publications: (PMID: 22481384) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Myoglobinuria, acute recurrent, autosomal recessive Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jan 13, 2022 | - - |
Acute Recurrent Myoglobinuria Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 4
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at