ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.490T>G (p.Leu164Val)

dbSNP: rs1279014555
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000824544 SCV005375427 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2024-06-13 reviewed by expert panel curation The c.490T>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Leucine by Valine at amino acid 164 (p.Leu164Val). The highest population minor allele frequency in gnomAD v4 is 0.00002519 (1/39698 alleles) in the East Asian population, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting, meeting this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD. To our knowledge, this variant has not been reported in the literature in individuals affected with SCID/DCLRE1C-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM2_Supporting (VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp RCV000824544 SCV000965445 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2018-07-09 criteria provided, single submitter clinical testing 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. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DCLRE1C-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with valine at codon 164 of the DCLRE1C protein (p.Leu164Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine.

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