ClinVar

Description

Variant summary: The PALB2 c.1383T>A (p.Ser461Arg) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index), however these predictions were not evaluated for functional impact by in vivo/vitro studies. This variant was found in 5/276698 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.0145% (5/34408). This frequency is similar to the estimated maximal expected allele frequency of a pathogenic PALB2 variant (0.01563%), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant of interest has been reported in affected individual(s) (Lu 2015), however without evidence for causality (i.e. lack of family history information and co-occurrence data). In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.