Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000116058 | SCV000149967 | likely benign | not specified | 2014-02-15 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Illumina Laboratory Services, |
RCV000401033 | SCV000448467 | benign | Pancreatic cancer, susceptibility to, 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
KCCC/NGS Laboratory, |
RCV000401033 | SCV004016522 | likely benign | Pancreatic cancer, susceptibility to, 1 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001356526 | SCV004151232 | benign | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | PALLD: BS1, BS2 |
Department of Pathology and Laboratory Medicine, |
RCV001356526 | SCV001551725 | likely benign | not provided | no assertion criteria provided | clinical testing | The PALLD p.Arg255His variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs146018183), ClinVar (classified as likely benign by GeneDx and Illumina for pancreatic cancer) and LOVD 3.0 (classified as likely benign). The variant was also identified in control databases in 481 of 281742 chromosomes (1 homozygous) at a frequency of 0.001707 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 35 of 10312 chromosomes (freq: 0.003394), European (non-Finnish) in 355 of 128284 chromosomes (freq: 0.002767), European (Finnish) in 47 of 25098 chromosomes (freq: 0.001873), Other in 13 of 7188 chromosomes (freq: 0.001809), Latino in 20 of 35410 chromosomes (freq: 0.000565), African in 10 of 24922 chromosomes (freq: 0.000401) and South Asian in 1 of 30580 chromosomes (freq: 0.000033), but was not observed in the East Asian population. The p.Arg255 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |