Submissions for variant NM_001375808.2(LPIN2):c.1169-3C>T

gnomAD frequency: 0.00011  dbSNP: rs200259086

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001702639	SCV000513505	likely benign	not provided	2021-01-14	criteria provided, single submitter	clinical testing
Invitae	RCV000553003	SCV000645159	uncertain significance	Majeed syndrome	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change falls in intron 7 of the LPIN2 gene. It does not directly change the encoded amino acid sequence of the LPIN2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200259086, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with LPIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 378093). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Laboratory Services, Illumina	RCV000553003	SCV001281369	uncertain significance	Majeed syndrome	2018-01-12	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252120	SCV002523669	uncertain significance	See cases	2020-01-22	criteria provided, single submitter	clinical testing	ACMG classification criteria: PM2, BP4
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263673	SCV002543521	uncertain significance	Autoinflammatory syndrome	2019-07-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902480	SCV004723129	likely benign	LPIN2-related disorder	2020-02-03	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).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702639	SCV001933024	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702639	SCV001972840	likely benign	not provided		no assertion criteria provided	clinical testing