ClinVar Miner

Submissions for variant NM_206933.4(USH2A):c.3317-2A>G

gnomAD frequency: 0.00001  dbSNP: rs2034951427
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001075303 SCV001240920 pathogenic Retinal dystrophy 2017-12-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001386858 SCV001587240 pathogenic not provided 2024-09-22 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 16 of the USH2A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH2A are known to be pathogenic (PMID: 10729113, 10909849, 20507924, 25649381). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Usher syndrome (PMID: 17405132). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 866916). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001828541 SCV002768377 pathogenic Usher syndrome type 2A 2021-05-06 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 retinitis pigmentosa 39 (MIM#6138093) and type 2A Usher syndrome (MIM#276901). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3: 1 heterozygote, 0 homozygotes). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another canonical splice site variant comparable to the one identified in this case has limited previous evidence for pathogenicity (ClinVar, PMID: 27460420). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals with retinitis pigmentosa and Usher syndrome (ClinVar, PMIDs: 17405132, 23591405, 27460420). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Genome-Nilou Lab RCV003446614 SCV004172162 pathogenic Retinitis pigmentosa 39 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001828541 SCV004172163 pathogenic Usher syndrome type 2A 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001828541 SCV002093935 pathogenic Usher syndrome type 2A 2020-08-10 no assertion criteria provided clinical testing

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