ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.406G>A (p.Asp136Asn)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV001267665 SCV001445892 likely pathogenic Severe combined immunodeficiency disease 2019-07-10 criteria provided, single submitter clinical testing Although this variant has not been reported in an affected patient in the literature, the p.Asp136Asn variant has been mutated in an in vitro and in vivo model. The experiments showed that the Asp136Asn mutatant's ability to support V(D)J recombination was abolished (PMID: 15071507). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.406G>A (p.Asp136Asn) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.406G>A (p.Asp136Asn) variant is classified as Likely Pathogenic.
Invitae RCV001349774 SCV001544134 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2020-10-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 136 of the DCLRE1C protein (p.Asp136Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with severe combined immunodeficiency (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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