ClinVar Miner

Submissions for variant NM_001375808.2(LPIN2):c.2547-1G>A

gnomAD frequency: 0.00001  dbSNP: rs145858312
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778530 SCV000914813 uncertain significance Majeed syndrome 2018-11-05 criteria provided, single submitter clinical testing The LPIN2 c.2547-1G>A variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. This variant is reported at a frequency of 0.000227 in the African American population of the Exome Sequencing Project, but this frequency is based on one allele in a region of good sequencing coverage. The variant is thus presumed to be rare. Based on the potential impact of splice acceptor variants and the lack of clarifying evidence, the c.2547-1G>A variant is classified as of uncertain significance but suspicious for pathogenicity for Majeed syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV000778530 SCV001410709 uncertain significance Majeed syndrome 2019-09-03 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in the last intron (intron 19) of the LPIN2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs145858312, ExAC 0.01%). This variant has not been reported in the literature in individuals with LPIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 631799). Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Fulgent Genetics, Fulgent Genetics RCV000778530 SCV002791706 uncertain significance Majeed syndrome 2022-05-12 criteria provided, single submitter clinical testing

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