ClinVar Miner

Submissions for variant NM_002582.4(PARN):c.709C>T (p.Arg237Ter)

dbSNP: rs760506977
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Godley laboratory, The University of Chicago RCV001252646 SCV001194308 pathogenic Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 2020-04-06 criteria provided, single submitter clinical testing This heterozygous variant was found in germline in a proband with macrocytosis (age 47) and ILD/UIP (age 52) and segregates with disease in three 2nd degree genotype positive family members (macrocytosis (1), ILD (3)). The following ACMG/AMP criteria were applied: PVS1, PM2, PP3, PP1.
Labcorp Genetics (formerly Invitae), Labcorp RCV001201968 SCV001373063 pathogenic Dyskeratosis congenita, autosomal recessive 6; Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4 2024-02-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg237*) in the PARN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PARN are known to be pathogenic (PMID: 9736620, 25848748, 26810774). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with dyskeratosis congenita asssociated Hoyeraal-Hreidarsson syndrome (PMID: 26810774). ClinVar contains an entry for this variant (Variation ID: 933700). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago RCV001819891 SCV002069309 pathogenic not provided 2019-01-09 criteria provided, single submitter clinical testing DNA sequence analysis of the PARN gene demonstrated a sequence change, c.709C>T, which results in the creation of a premature stop codon at amino acid position 237, p.Arg237*. This pathogenic sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated PARN protein with potentially abnormal function. This pathogenic sequence change has previously been described in the heterozygous state in a patient with fibrosing nonspecific interstitial pneumonia (Petrovski et al., 2017) and in the compound heterozygous state with a second pathogenic sequence change in a patient with Hoyeraal-Hreidarsson syndrome (Burris et al., 2016).

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