ClinVar Miner

Submissions for variant NM_014646.2(LPIN2):c.991G>T (p.Ala331Ser) (rs80338805)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000223474 SCV000279000 likely benign not specified 2018-02-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000020710 SCV000604121 uncertain significance Majeed syndrome 2019-05-09 criteria provided, single submitter clinical testing The LPIN2 c.991G>T; p.Ala331Ser variant (rs80338805) has been described in the InFevers database in an individual with psoriasis and in the literature in an individual with a periodic fever syndrome (see link to database, Hurtado-Nedelec 2010), but also as enriched in the Spanish population (Dopazo 2016). The variant is reported in the ClinVar database (Variation ID: 21520), and in the Latino population with an allele frequency of 0.4% (147/34416 alleles, including 1 homozygote) in the Genome Aggregation Database. GeneReviews lists this variant as a benign LPIN2 variant without a reference (see link to GeneReviews). The alanine at codon 331 is moderately conserved across species and computational programs (PolyPhen-2, SIFT) predict this is tolerated. Due to conflicting information, the clinical significance of the variant is uncertain at this time. References: Link to LPIN2 Ala331Ser variant in database: http://fmf.igh.cnrs.fr/ISSAID/infevers/detail_mutation.php Link to Majeed Syndrome GeneReviews: https://www.ncbi.nlm.nih.gov/books/NBK1974/ Dopazo J et al. 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation. Mol Biol Evol. 2016. 33(5):1205-18. Hurtado-Nedelec M et al. Genetic susceptibility factors in a cohort of 38 patients with SAPHO syndrome: a study of PSTPIP2, NOD2, and LPIN2 genes. J Rheumatol. 2010. 37(2):401-9.
Invitae RCV000020710 SCV000645179 likely benign Majeed syndrome 2019-12-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000755296 SCV000892503 likely benign not provided 2018-07-01 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000020710 SCV000898800 uncertain significance Majeed syndrome 2018-05-25 criteria provided, single submitter clinical testing LPIN2 NM_014646.2 exon 7 p.Ala331Ser (c.991G>T): This variant has been reported in the Hereditary Auto-inflammatory Disorders database in 1 individual with psoriasis (http://fmf.igh.cnrs.fr/ISSAID/infevers/). However, this variant is present in 0.4% (147/34416) of Latino alleles, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs80338805). This variant is present in ClinVar (Variation ID:21520). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Illumina Clinical Services Laboratory,Illumina RCV000020710 SCV001286116 benign Majeed syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneReviews RCV000020710 SCV000041269 benign Majeed syndrome 2008-09-23 no assertion criteria provided curation Converted during submission to Benign.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000020710 SCV000116195 not provided Majeed syndrome no assertion provided not provided

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