ClinVar

Description

The ACD p.Gly387Arg variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs553014261) and in control databases in 17 of 227966 chromosomes (1 homozygous) at a frequency of 0.00007457 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 8 of 18768 chromosomes (freq: 0.000426), African in 6 of 24118 chromosomes (freq: 0.000249), Latino in 1 of 26912 chromosomes (freq: 0.000037) and European (non-Finnish) in 2 of 107624 chromosomes (freq: 0.000019), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or Other populations. The p.Gly387 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, 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.