Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001394898 | SCV001596591 | likely benign | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001581116 | SCV001821329 | likely benign | not specified | 2021-08-20 | criteria provided, single submitter | clinical testing | Variant summary: RPGRIP1 c.2725A>G (p.Thr909Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 280646 control chromosomes, predominantly at a frequency of 0.0025 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in RPGRIP1 causing Leber Congenital Amaurosis phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. c.2725A>G has been reported in the literature in at least one individual affected with Leber Congenital Amaurosis (Zernant_2005). The report does not provide unequivocal conclusions about association of the variant with Leber Congenital Amaurosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |