ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.2173A>G (p.Asn725Asp)

gnomAD frequency: 0.00009  dbSNP: rs373201651
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000636953 SCV000758401 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 725 of the RPGRIP1L protein (p.Asn725Asp). This variant is present in population databases (rs373201651, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 530897). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002529857 SCV003601380 likely benign Inborn genetic diseases 2022-09-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics, part of Exact Sciences RCV003411511 SCV004113237 uncertain significance RPGRIP1L-related condition 2022-12-08 criteria provided, single submitter clinical testing The RPGRIP1L c.2173A>G variant is predicted to result in the amino acid substitution p.Asn725Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-53683007-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001835889 SCV002085699 uncertain significance Familial aplasia of the vermis 2020-09-10 no assertion criteria provided clinical testing

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