Submissions for variant NM_001375808.2(LPIN2):c.2621G>T (p.Cys874Phe)

dbSNP: rs201160155

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000658798	SCV000279016	likely benign	not provided	2019-12-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000274408	SCV000408470	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.
CeGaT Center for Human Genetics Tuebingen	RCV000658798	SCV000780593	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	LPIN2: BS2
Fulgent Genetics, Fulgent Genetics	RCV000274408	SCV000896694	uncertain significance	Majeed syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000274408	SCV001018602	benign	Majeed syndrome	2024-01-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000274408	SCV001477648	uncertain significance	Majeed syndrome	2021-09-13	criteria provided, single submitter	clinical testing	The LPIN2 c.2621G>T; p.Cys874Phe variant (rs201160155), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is reported in the ClinVar database (Variation ID: 234343) and in the South Asian population with an allele frequency of 0.9% (280/30614 alleles, including 3 homozygotes) in the Genome Aggregation database. This is a missense variant in a moderately conserved amino acid and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.362). 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.Cys874Phe variant is uncertain at this time.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262820	SCV002543268	likely benign	Autoinflammatory syndrome	2022-03-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947730	SCV004758368	benign	LPIN2-related disorder	2020-06-26	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).