ClinVar

Description

The ARX c.333_335dupGGC variant is predicted to result in an in-frame duplication (p.Ala115dup). This variant was reported as a maternally-inherited variant in two unrelated male individuals with intellectual disability/developmental delay (reported as c.333_334ins(GCG) in patients #39589 and #41263, Gronskov et al. 2004. PubMed ID: 15199382). However, this variant was not found in a similarly affected family member of the patient #39589 but was identified in an unaffected male control in the same study, suggested by the author that this variant is a rare polymorphism. This variant is reported in 0.078% of alleles in individuals of African descent in gnomAD and has been documented in a hemizygous individual (http://gnomad.broadinstitute.org/variant/X-25031776-T-TGCC). In ClinVar, this variant has conflicting interpretations ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/157755/). This variant falls within a low complexity region, therefore the allele frequency data should be interpreted with caution. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.