ClinVar Miner

Submissions for variant NM_020320.5(RARS2):c.1340_1365del (p.Phe447fs)

dbSNP: rs1064795060
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483947 SCV000570495 likely pathogenic not provided 2016-05-23 criteria provided, single submitter clinical testing The c.1340_1365del26 variant in the RARS2 gene has not been observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.1340_1365del26 variant causes a frameshift starting with codon Phenylalanine 447, changes the amino acid to a Serine residue and creates a premature Stop codon at position 29 of the new reading frame, denoted p.F447SfsX29. This variant is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. Although this variant has not been reported previously to our knowledge, other frameshift and loss of function variants downstream of this position have been reported in the Human Gene Mutation Database in association with RARS2-related disorders (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however the possibility that it is benign cannot be excluded.
Invitae RCV000483947 SCV001583769 pathogenic not provided 2023-09-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe447Serfs*29) in the RARS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RARS2 are known to be pathogenic (PMID: 17847012, 22569581, 26083569). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 421326). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003464019 SCV004206132 likely pathogenic Pontocerebellar hypoplasia type 6 2023-10-23 criteria provided, single submitter clinical testing

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