ClinVar Miner

Submissions for variant NM_001330078.2(NRXN1):c.2497+3A>G (rs202074070)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725752 SCV000241882 uncertain significance not provided 2016-08-22 criteria provided, single submitter clinical testing The c.2617+3 A>G variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In silico analysis predicts this variant damages the natural splice donor site in intron 14, which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of the c.2617+3 A>G sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725752 SCV000339183 uncertain significance not provided 2016-01-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000188272 SCV000614360 uncertain significance not specified 2016-10-20 criteria provided, single submitter clinical testing
Invitae RCV000802683 SCV000942524 uncertain significance Pitt-Hopkins-like syndrome 2 2018-07-05 criteria provided, single submitter clinical testing This sequence change falls in intron 14 of the NRXN1 gene. It does not directly change the encoded amino acid sequence of the NRXN1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NRXN1-related disease. ClinVar contains an entry for this variant (Variation ID: 206243). 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.

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