Submissions for variant NM_001375808.2(LPIN2):c.2625G>A (p.Pro875=)

gnomAD frequency: 0.00025  dbSNP: rs187572602

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001200412	SCV000279535	likely benign	not provided	2019-04-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000368839	SCV000408469	likely benign	Majeed syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000368839	SCV000898797	uncertain significance	Majeed syndrome	2021-03-30	criteria provided, single submitter	clinical testing	LPIN2 NM_014646.2 exon 20 p.Pro875= (c.2625G>A): This variant has not been reported in the literature but is present in 0.5% (102/18858) of East Asian alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs187572602). This variant is present in ClinVar (Variation ID:234588). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. However, splice prediction tools suggest that this variant may create a novel splice site; further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae	RCV000368839	SCV001005051	benign	Majeed syndrome	2024-01-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001200412	SCV001371365	likely benign	not provided	2020-05-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000368839	SCV002049682	uncertain significance	Majeed syndrome	2021-04-30	criteria provided, single submitter	clinical testing	The LPIN2 c.2625G>A; p.Pro875= variant (rs187572602), to our knowledge, is not reported in the literature, but is reported in a database in an individual with autoinflammatory disease (see link below). The variant is listedin the ClinVar database (Variation ID: 234588) and is reported in the East Asian population with an allele frequency of 0.5% (108/19,940 alleles including 1 homozygote) in the Genome Aggregation Database. This is a synonymous variant in a weakly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic acceptor splice site. While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of the p.Pro875= variant is uncertain at this time. References: Link to Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=7
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262828	SCV002543572	likely benign	Autoinflammatory syndrome	2020-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003967606	SCV004785168	likely benign	LPIN2-related disorder	2021-07-03	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001200412	SCV001797371	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001200412	SCV001966733	likely benign	not provided		no assertion criteria provided	clinical testing