Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000264185 | SCV000479768 | uncertain significance | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2017-04-27 | criteria provided, single submitter | clinical testing | The GALT c.904+2T>G variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium despite being located in a region of good sequencing coverage. Therefore, the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for galactosemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Labcorp Genetics |
RCV000264185 | SCV005764743 | pathogenic | Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase | 2025-01-15 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 9 of the GALT gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367). This variant is present in population databases (no rsID available, gnomAD 0.007%). Disruption of this splice site has been observed in individuals with galactosemia (PMID: 28173647, 29653003). ClinVar contains an entry for this variant (Variation ID: 366701). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |