ClinVar

Description

The RAG2 p.Val272Ile variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs117899975) and in Cosmic (confirmed somatically in pancreas carcinoma tumour sample; FATHMM prediction of pathogenic, score 0.95). The variant was also identified in control databases in 48 of 282752 chromosomes at a frequency of 0.00017 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 35 of 19948 chromosomes (freq: 0.001755), South Asian in 12 of 30616 chromosomes (freq: 0.000392) and European (non-Finnish) in 1 of 129116 chromosomes (freq: 0.000008), but was not observed in the African, Latino, Ashkenazi Jewish, European (Finnish) or Other populations. The p.Val272 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; 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. This variant is classified as a variant of uncertain significance.