Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| National Institute on Deafness and Communication Disorders, |
RCV001328033 | SCV001519368 | uncertain significance | Childhood onset hearing loss | 2021-07-08 | criteria provided, single submitter | research | PS3_moderate, PP3 / Modifications from PMID: 30311386 for classification: The genetic causes of hearing loss have not yet been well characterized in the Yoruba population, and the information regarding variant MAF in this population is still limited, so we did not exclude any variant based on their "high" MAF. PP3 criteria was applied even if the REVEL score was below 0.7, if at least two of the pathogenicity prediction algorithms used predicted that the variant was damaging or likely damaging. |
| Gene |
RCV001564155 | SCV001787270 | uncertain significance | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing | Observed in multiple unrelated individuals with hypogonadotrophic hypogonadism; the variant was inherited from an unaffected mother in one family, and another family also harbored a frameshift variant in the FGFR1 gene (Kim et al., 2008; Zhang et al., 2019; Cassatella et al., 2018; Xu et al., 2018); Published functional studies confirm variant results in skipping of exon 8, and is predicted to result in a frameshift and subsequent protein truncation (Kim et al., 2008); This variant is associated with the following publications: (PMID: 29144511, 29419413, 18834967) |
| Invitae | RCV001851572 | SCV002143091 | uncertain significance | CHARGE syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 of the CHD7 gene. It does not directly change the encoded amino acid sequence of the CHD7 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with hypogonadotropic hypogonadism (PMID: 18834967, 29419413, 34837038). This variant is also known as IVS8+5G>A. ClinVar contains an entry for this variant (Variation ID: 2035). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 8 and introduces a premature termination codon (PMID: 18834967). The resulting mRNA is expected to undergo nonsense-mediated decay. 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. |
| Fulgent Genetics, |
RCV002490295 | SCV002800768 | uncertain significance | CHARGE syndrome; Hypogonadotropic hypogonadism 5 with or without anosmia | 2022-04-13 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002512666 | SCV003549198 | likely benign | Inborn genetic diseases | 2021-08-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| OMIM | RCV000030871 | SCV000022273 | pathogenic | Hypogonadotropic hypogonadism 5 with or without anosmia | 2008-10-01 | no assertion criteria provided | literature only |