Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000413948 | SCV000491816 | likely pathogenic | not provided | 2016-12-01 | criteria provided, single submitter | clinical testing | The c.716+5G>A variant in the SLC13A5 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant destroys the splice donor site in intron 5, and is expected to cause abnormal gene splicing. The c.716+5G>A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.716+5G>A as a likely pathogenic variant. |
| Broad Center for Mendelian Genomics, |
RCV001764344 | SCV001999884 | uncertain significance | Developmental and epileptic encephalopathy, 25 | 2021-11-02 | criteria provided, single submitter | curation | The c.716+5G>A variant in SLC13A5 has been reported in 1 homozygous individual with developmental and epileptic encephalopathy (PMID: 31487502) and has been identified in in 0.003% (1/30568) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1057518298). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 373237) and has been interpreted as likely pathogenic by GeneDx. This variant is located in the 3' splice region. Computational tools do suggest an impact to splicing. However, this information is not predictive enough to determine/rule out pathogenicity. In summary, the clinical significance of the c.716+5G>A variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PM3_supporting, PP3 (Richards 2015). |