Total submissions: 13
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Medicine Center of Excellence, |
RCV000003864 | SCV005438297 | uncertain significance | UDPglucose-4-epimerase deficiency | 2024-12-18 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000592410 | SCV005410423 | uncertain significance | not provided | 2023-07-17 | criteria provided, single submitter | clinical testing | BS1 |
| Laboratory for Molecular Medicine, |
RCV000609606 | SCV004847446 | likely benign | not specified | 2024-02-21 | criteria provided, single submitter | clinical testing | The p.Lys257Arg variant in GALE is classified as likely benign because it has been identified in 1.9% (1474/75008) of African chromosomes, including 24 total homozygotes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1. |
| Ce |
RCV000592410 | SCV004700471 | benign | not provided | 2025-04-01 | criteria provided, single submitter | clinical testing | GALE: BS1, BS2 |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000592410 | SCV003799128 | uncertain significance | not provided | 2022-10-19 | criteria provided, single submitter | clinical testing | PS3_Supporting, BA1 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000609606 | SCV002500159 | benign | not specified | 2022-03-07 | criteria provided, single submitter | clinical testing | Variant summary: GALE c.770A>G (p.Lys257Arg) results in a conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 248990 control chromosomes, predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 17 fold of the estimated maximal expected allele frequency for a pathogenic variant in GALE causing UDPglucose-4-Epimerase Deficiency phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a majority consensus as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
| Mendelics | RCV000003864 | SCV001135217 | likely benign | UDPglucose-4-epimerase deficiency | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000609606 | SCV000730667 | likely benign | not specified | 2018-02-01 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Eurofins Ntd Llc |
RCV000592410 | SCV000700362 | other | not provided | 2017-07-14 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000003864 | SCV000636278 | benign | UDPglucose-4-epimerase deficiency | 2019-12-22 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004752683 | SCV005357664 | uncertain significance | GALE-related disorder | 2024-09-13 | no assertion criteria provided | clinical testing | The GALE c.770A>G variant is predicted to result in the amino acid substitution p.Lys257Arg. This variant has been reported in several peripheral epimerase deficiency galactosemia patients (Maceratesi et al. 1998. PubMed ID: 9538513; Openo et al. 2006. PubMed ID: 16385452). However, none of these patients had a second clearly pathogenic GALE variant, and the reported results of in vitro and in vivo studies of the c.770A>G variant are conflicting (Timson 2005. PubMed ID: 16302980; Wasilenko et al. 2005. PubMed ID: 15639193). The c.770A>G variant has been documented with a minor allele frequency of ~2% in an African population, which is high for a pathogenic variant. Although we suspect that this variant is probably benign, its clinical significance is currently uncertain due to the absence of conclusive functional and genetic evidence. |
| Gene |
RCV000003864 | SCV000040659 | pathogenic | UDPglucose-4-epimerase deficiency | 2021-02-24 | no assertion criteria provided | literature only | Assoc with asymptomatic peripheral epimerase deficiency galactosemia in African Americans |
| OMIM | RCV000003864 | SCV000024029 | pathogenic | UDPglucose-4-epimerase deficiency | 1998-01-01 | no assertion criteria provided | literature only |