Submissions for variant NM_020366.4(RPGRIP1):c.930+3A>G

gnomAD frequency: 0.00419  dbSNP: rs150107283

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000417812	SCV000516755	likely benign	not specified	2017-01-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Center for Human Genetics Tuebingen	RCV000585329	SCV000692781	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	RPGRIP1: BP4, BS1, BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083158	SCV001098110	benign	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2024-01-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113068	SCV001270806	likely benign	Cone-rod dystrophy 13	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001113069	SCV001270807	uncertain significance	Leber congenital amaurosis 6	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000585329	SCV001474597	uncertain significance	not provided	2019-07-22	criteria provided, single submitter	clinical testing	The RPGRIP1 c.930+3A>G variant (rs150107283) is reported in the medical literature in an individual with Leber congenital amaurosis (Astuti 2015). The variant is reported in the ClinVar database (Variation ID: 379572). This variant is found in the Finnish European population with an overall allele frequency of 1.8% (406/22244 alleles, including 8 homozygotes) in the Genome Aggregation Database. This is an intronic variant that is not part of the canonical donor site, the nucleotide at this position is conserved, and computational analyses (Alamut v.2.11) predict that this variant weakens the upstream donor site. Although the allele frequency is relatively high, there is insufficient clinical evidence to classify this variant with certainty. Pathogenic RPGRIP1 variants are causative for autosomal recessive Leber congenital amaurosis (MIM: 613826) or autosomal recessive cone-rod dystrophy (MIM:608194).
PreventionGenetics, part of Exact Sciences	RCV003932581	SCV004753312	likely benign	RPGRIP1-related disorder	2019-06-21	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).