ClinVar Miner

Submissions for variant NM_000180.4(GUCY2D):c.2101C>T (p.Pro701Ser)

gnomAD frequency: 0.03505  dbSNP: rs34598902
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen RCV005053894 SCV005687740 benign GUCY2D-related recessive retinopathy 2025-01-30 reviewed by expert panel curation NM_000180.4(GUCY2D):c.2101C>T (p.Pro701Ser) is a missense variant that is predicted to replace proline at position p.701 with serine. This variant is present in gnomAD v.4.1.0 at a Grpmax allele frequency of 0.2041, with 9318 / 44874 alleles in the East Asian population, which is higher than the ClinGen LCA / eoRD VCEP BA1 threshold of >0.016 (BA1). This variant has been found in the homozygous state in 2099 adult individuals in gnomAD which exceeds the LCA/eoRD VCEP threshold of >6 (gnomAD version 4.1.0; BS2). The computational predictor REVEL gives a score of 0.27, which is below the ClinGen LCA / eoRD VCEP threshold of <0.290 and predicts a non-damaging effect on RetGC-1 protein function. In addition, the splicing impact predictor SpliceAI gives a delta score of 0, which is below the ClinGen LCA/eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4). In summary, this variant meets the criteria to be classified as Benign for GUCY2D-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA/eoRD VCEP:BA1, BS2, BP4 (VCEP specifications version 1.0.0; date of approval 01/22/2025).
Eurofins Ntd Llc (ga) RCV000173653 SCV000224788 benign not specified 2014-10-03 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000173653 SCV000302885 likely benign not specified criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000173653 SCV000539262 benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 180/2178=8.2%
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000084851 SCV001157142 benign not provided 2023-11-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001518412 SCV001727098 benign Cone-rod dystrophy 6; Leber congenital amaurosis 1 2025-02-03 criteria provided, single submitter clinical testing
GeneDx RCV000084851 SCV001895586 benign not provided 2018-11-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27884173, 11035546, 23424971, 20981092, 18055820, 15111605)
Fulgent Genetics, Fulgent Genetics RCV002498446 SCV002807163 benign Choroidal dystrophy, central areolar, 1; Cone-rod dystrophy 6; Leber congenital amaurosis 1; Night blindness, congenital stationary, type1i 2021-09-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004815025 SCV005072132 benign Retinal dystrophy 2018-01-01 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV000084851 SCV005218693 likely benign not provided criteria provided, single submitter not provided
Retina International RCV000084851 SCV000116987 not provided not provided no assertion provided not provided
Department of Ophthalmology and Visual Sciences Kyoto University RCV000084851 SCV000172506 probable-non-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely benign.
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV001250835 SCV001426325 likely benign Leber congenital amaurosis 1 no assertion criteria provided research

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