Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002169582 | SCV002337025 | likely benign | Hereditary pancreatitis | 2023-08-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002169582 | SCV002724223 | uncertain significance | Hereditary pancreatitis | 2014-06-23 | criteria provided, single submitter | clinical testing | The c.200+18G>A intronic variant results from a G to A substitution 18 nucleotides after coding exon 2 in the PRSS1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this donor splice site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331280 | SCV004037890 | uncertain significance | not specified | 2023-08-04 | criteria provided, single submitter | clinical testing | Variant summary: PRSS1 c.200+18G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3.2e-05 in 251054 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.200+18G>A in individuals affected with Chronic Pancreatitis and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |