Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001147458 | SCV001308284 | 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. |
| Ambry Genetics | RCV004032754 | SCV003855661 | uncertain significance | not specified | 2024-11-21 | criteria provided, single submitter | clinical testing | The p.A186T variant (also known as c.556G>A), located in coding exon 1 of the PALLD gene, results from a G to A substitution at nucleotide position 556. The alanine at codon 186 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV001147458 | SCV005657683 | uncertain significance | Pancreatic cancer, susceptibility to, 1 | 2024-06-05 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001357988 | SCV001553606 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The PALLD p.Ala186Thr variant was not identified in the literature nor was it identified in ClinVar or Cosmic. The variant was identified in dbSNP (ID: rs139434937), LOVD 3.0 and in control databases in 41 of 282196 chromosomes at a frequency of 0.000145 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 19 of 30610 chromosomes (freq: 0.000621), European (non-Finnish) in 16 of 128620 chromosomes (freq: 0.000124), Latino in 4 of 35420 chromosomes (freq: 0.000113), African in 1 of 24934 chromosomes (freq: 0.00004) and European (Finnish) in 1 of 25124 chromosomes (freq: 0.00004), while the variant was not observed in the Ashkenazi Jewish, East Asian or Other populations. 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. The p.Ala186 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |