ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.291T>C (p.Asp97=)

gnomAD frequency: 0.00001  dbSNP: rs1840574128
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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 RCV001482925 SCV005375432 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2024-06-13 reviewed by expert panel curation The c.291T>C (NM_001033855.3) variant in the DCLRE1C gene is a synonymous variant (p.Asp97=). The filtering allele frequency (the upper threshold of the 95% CI of 2/44736 alleles) of the c.291T>C variant in DCLRE1C is 0.000007410 for East Asian chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD. According to at least two in silico tools (SpliceAI and varSEAK), this synonymous variant was not predicted to impact the consensus sequence or create a new site (BP7). 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, due to conflict evidence, 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 and BP7(VCEP specifications version 1).
Labcorp Genetics (formerly Invitae), Labcorp RCV001482925 SCV001687305 likely benign Severe combined immunodeficiency due to DCLRE1C deficiency 2024-10-02 criteria provided, single submitter clinical testing

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