Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003512707 | SCV004333902 | pathogenic | Borjeson-Forssman-Lehmann syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg116*) in the PHF6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHF6 are known to be pathogenic (PMID: 12415272, 24092917, 25099957, 26648834). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Borjeson-Forssman-Lehmann syndrome (PMID: 27698851, 35662002). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. |
| Victorian Clinical Genetics Services, |
RCV003512707 | SCV005086282 | pathogenic | Borjeson-Forssman-Lehmann syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Borjeson-Forssman-Lehmann syndrome (MIM# 301900) in males; females heterozygous for pathogenic variants show an overlapping but distinct phenotype (PMID: 35662002). (I) 0109 - This gene is associated with X-linked recessive disease in males. Female with heterozygous variants may be affected; variant type and skewed X-inactivation may contribute to gender-specific phenotypes (PMID: 35662002). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0702 - Other NMD-predicted variants comparable to the one identified in this case have strong previous evidence for pathogenicity in heterozygous females (PMIDs: 35662002, 34041787). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been observed in two heterozygous females with Borjeson-Forssman-Lehmann syndrome, with de novo inheritance reported in one (PMIDs: 35662002, 36999477). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |