Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001192440 | SCV001360558 | benign | not specified | 2019-10-01 | criteria provided, single submitter | clinical testing | Variant summary: PRSS1 c.200+17C>T 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. 5/5 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 0.0041 in 229856 control chromosomes (gnomAD). The observed variant frequency is approximately 820 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRSS1 causing Chronic Pancreatitis Risk phenotype (5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.200+17C>T in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating the variant's impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. |
Labcorp Genetics |
RCV002069200 | SCV002374118 | likely benign | Hereditary pancreatitis | 2025-01-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002069200 | SCV002721562 | benign | Hereditary pancreatitis | 2016-01-11 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |