ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.662A>C (p.Tyr221Ser) (rs764571295)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Institute Rare Disease Group, Broad Institute RCV000678441 SCV001164361 uncertain significance Neuronal ceroid lipofuscinosis 6 2018-12-03 criteria provided, single submitter research The homozygous p.Tyr221Ser variant in CLN6 was identified by our study in one individual with neuronal ceroid lipofuscinosis. The p.Tyr221Ser variant in CLN6 has been reported in 1 Argentinian individual and 1 Turkish Individual with neuronal ceroid lipofuscinosis (PMID: 12815591, 21990111), and has been identified in 0.01624% (5/30782) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs764571295). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. This missense variant affects the same residue as a variant, p.Tyr221Cys, reported in association with neuronal ceroid lipofuscinosis in 2 siblings and 1 unrelated individual in the literature, slightly supporting that a change at this residue may not be tolerated (PMID: 19135028). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PM5_Supporting (Richards 2015).
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000678441 SCV001251822 pathogenic Neuronal ceroid lipofuscinosis 6 2020-05-03 criteria provided, single submitter clinical testing
Translational Research Program on Neuronal Ceroid Lipofuscinosis,Center for the Study of Inborn Errors of Metabolism RCV000678441 SCV000804308 pathogenic Neuronal ceroid lipofuscinosis 6 no assertion criteria provided research Late Infantile NCL

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