Submissions for variant NM_001166108.2(PALLD):c.731A>G (p.Gln244Arg)

gnomAD frequency: 0.00143  dbSNP: rs114946738

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000116057	SCV000149966	uncertain significance	not provided	2014-02-25	criteria provided, single submitter	clinical testing	PALLD has been only recently described in association with cancer predisposition and the risks are not well understood. This variant is denoted PALLD c.731A>G at the cDNA level, p.Gln244Arg (Q244R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PALLD Gln244Arg was observed in multiple subpopulations, with the highest allele frequency of 0.45% in individuals of African ancestry within 1000 Genomes. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution and may affect protein integrity. PALLD Gln244Arg occurs at a position that is moderately conserved across species and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the PALLD gene, remain unclear.
Illumina Laboratory Services, Illumina	RCV000359984	SCV000448466	benign	Pancreatic cancer, susceptibility to, 1	2018-01-12	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.
PreventionGenetics, part of Exact Sciences	RCV003905106	SCV004725624	likely benign	PALLD-related condition	2020-01-07	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).