ClinVar

Description

The ABCC2 p.Leu1183Met variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs145008610), ClinVar (classified as a VUS by EGL Genetics) and LOVD 3.0. The variant was also identified in control databases in 18 of 282898 chromosomes at a frequency of 0.000064 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 7228 chromosomes (freq: 0.000138) and European (non-Finnish) in 17 of 129194 chromosomes (freq: 0.000132); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The p.Leu1183 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. 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.