ClinVar Miner

Submissions for variant NM_012208.4(HARS2):c.448C>T (p.Arg150Cys) (rs140540222)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199285 SCV000251608 likely pathogenic not provided 2021-09-28 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34406847, 31827252, 31449985)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000223531 SCV000271834 uncertain significance not specified 2016-05-01 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg150Cys variant in HARS2 has been reported by our laboratory in one individual with hea ring loss who was compound heterozygous for a second variant of uncertain signif icance in the HARS2 gene (this family). This variant has been identified in 6/1 21406 total chromosomes across all populations by the Exome Aggregation Consorti um (ExAC, http://exac.broadinstitute.org; dbSNP rs140540222). Although this vari ant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools suggest that the p.A rg150Cys variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Arg150Cys variant is uncertain.
Molecular Genetics Laboratory,University Hospital Copenhagen RCV000782169 SCV000920637 likely pathogenic Perrault syndrome 2 2019-05-20 no assertion criteria provided clinical testing Variant detected as compound heterozygous, together with c.172A>G in three siblings (two girls) with progressive sensorineural hearing impairment. Signs of premature ovarian failure were uncertain due to their young age. Variant detected as compound heterozygous, together with c.980G>A in a girl with progressive sensorineural hearing impairment. Signs of premature ovarian failure were uncertain due to her young age.

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