Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001213191 | SCV001384811 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-04-14 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 943078). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the SDHAF2 gene (p.Asn148Lysfs*34). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the SDHAF2 protein and extend the protein by 14 additional amino acid residues. |
Ambry Genetics | RCV003163622 | SCV003858382 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-26 | criteria provided, single submitter | clinical testing | The c.444_447delCAAA variant, located in coding exon 4 of the SDHAF2 gene, results from a deletion of 4 nucleotides at nucleotide positions 444 to 447, causing a translational frameshift with a predicted alternate stop codon (p.N148Kfs*34). This alteration occurs at the 3' terminus of theSDHAF2 gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 14 amino acids. This frameshift impacts the last 19 amino acidsamino acids of the native protein. The exact functional effect of the altered amino acids is unknown. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |