ClinVar

Description

Although the c.7132+2 T>C likely pathogenic variant in the FLNA gene has not been reported as a pathogenic variant or as a benign variant to our knowledge, it destroys the canonical splice donor site in intron 43 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Multiple other splice site variants in the FLNA gene have been reported in HGMD in association with periventricular heterotopia (Stenson et al., 2014). Furthermore, the c.7132+2 T>C variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, or in the Exome Aggregation Consortium (ExAC), indicating it is not a common benign variant in these populations.In summary, c.7132+2 T>C in the FLNA gene is expected to be pathogenic, as loss of function variants in this gene are strongly associated with this phenotype.