Submissions for variant NM_000388.4(CASR):c.1732+2T>C

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV005219781	SCV005859138	pathogenic	Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1	2024-04-26	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 6 of the CASR gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CASR-related conditions. 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 may disrupt the consensus splice site. This variant disrupts a region of the CASR protein in which other variant(s) (p.Arg886Pro) have been determined to be pathogenic (PMID: 11807402, 20798521). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.