ClinVar Miner

Submissions for variant NM_152383.5(DIS3L2):c.1722G>T (p.Glu574Asp)

gnomAD frequency: 0.00041  dbSNP: rs191608083
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000457169 SCV000551597 benign Perlman syndrome 2024-12-29 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821286 SCV002071996 uncertain significance not specified 2021-11-19 criteria provided, single submitter clinical testing DNA sequence analysis of the DIS3L2 gene demonstrated a sequence change, c.1722G>T, in exon 14 that results in an amino acid change, p.Glu574Asp. This sequence change has been described in the gnomAD database with a frequency of 0.038% in the non-Finnish European subpopulation (dbSNP rs191608083). The p.Glu574Asp change affects a poorly conserved amino acid residue located in a domain of the DIS3L2 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Glu574Asp substitution. This sequence change does not appear to have been previously described in individuals with DIS3L2-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Glu574Asp change remains unknown at this time.
Sema4, Sema4 RCV000457169 SCV002532402 uncertain significance Perlman syndrome 2021-08-13 criteria provided, single submitter curation
Ambry Genetics RCV002523345 SCV003688052 uncertain significance Inborn genetic diseases 2021-11-19 criteria provided, single submitter clinical testing The c.1722G>T (p.E574D) alteration is located in exon 14 (coding exon 13) of the DIS3L2 gene. This alteration results from a G to T substitution at nucleotide position 1722, causing the glutamic acid (E) at amino acid position 574 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV003480643 SCV004226021 uncertain significance not provided 2022-07-21 criteria provided, single submitter clinical testing BP4
Fulgent Genetics, Fulgent Genetics RCV000457169 SCV005656214 uncertain significance Perlman syndrome 2024-06-15 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000457169 SCV005689425 uncertain significance Perlman syndrome 2024-07-08 criteria provided, single submitter clinical testing The DIS3L2 c.1722G>T (p.Glu574Asp) missense change has a maximum subpopulation frequency of 0.038% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with Perlman syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000457169 SCV005912954 uncertain significance Perlman syndrome 2021-07-30 criteria provided, single submitter research

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