ClinVar Miner

Submissions for variant NM_015215.4(CAMTA1):c.2302T>C (p.Ser768Pro)

gnomAD frequency: 0.00014  dbSNP: rs201459076
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002548501 SCV003473523 uncertain significance not provided 2022-10-18 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1048960). This variant has not been reported in the literature in individuals affected with CAMTA1-related conditions. This variant is present in population databases (rs201459076, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 768 of the CAMTA1 protein (p.Ser768Pro).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354415 SCV001549028 benign not specified no assertion criteria provided clinical testing  The CAMTA1 p.S768P variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs201459076) and in control databases in 24 of 281974 chromosomes at a frequency of 0.00008511 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Latino in 18 of 35422 chromosomes (freq: 0.000508), Ashkenazi Jewish in 2 of 10356 chromosomes (freq: 0.000193), Other in 1 of 7214 chromosomes (freq: 0.000139) and European (non-Finnish) in 3 of 128406 chromosomes (freq: 0.000023), but was not observed in the African, East Asian, European (Finnish), or South Asian populations. The frequency is greater than expected for the rare autosomal dominant nonprogressive cerebellar ataxia with mental retardation disorder that is associated with CAMTA1 variants. The p.S768 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.

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