ClinVar Miner

Submissions for variant NM_172351.3(CD46):c.72G>A (p.Met24Ile)

gnomAD frequency: 0.00002  dbSNP: rs765047596
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Johns Hopkins Genomics, Johns Hopkins University RCV001543666 SCV001762352 uncertain significance Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly 2021-07-27 criteria provided, single submitter clinical testing CD46 c.72G>A (rs765047596) is rare (<0.1%) in a large population dataset (gnomAD: 1/251322 total alleles; 0.0004%; no homozygotes) and has not been reported in ClinVar nor the literature, to our knowledge. Three bioinformatic tools queried predict that this substitution would be tolerated and the methionine residue at this position is not evolutionarily conserved across the species assessed. We consider the clinical significance of CD46 c.72G>A to be uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV003771668 SCV004639257 uncertain significance not provided 2023-03-08 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with CD46-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 24 of the CD46 protein (p.Met24Ile). This variant is present in population databases (rs765047596, gnomAD 0.002%). ClinVar contains an entry for this variant (Variation ID: 1185016). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. 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.
Ambry Genetics RCV004897685 SCV005549879 uncertain significance not specified 2024-06-26 criteria provided, single submitter clinical testing The c.72G>A (p.M24I) alteration is located in exon 1 (coding exon 1) of the CD46 gene. This alteration results from a G to A substitution at nucleotide position 72, causing the methionine (M) at amino acid position 24 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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