ClinVar Miner

Submissions for variant NM_000293.3(PHKB):c.2896-1G>T

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003403028 SCV004121064 pathogenic PHKB-related disorder 2022-10-04 criteria provided, single submitter clinical testing The PHKB c.2875-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant can also be referred to as c.2896-1G>T with an alternative transcript (NM_000293). This variant in the compound heterozygous condition was reported in several individuals with glycogen storage disease type (reported as IVS30-1, Figure 4, van den Berg. 1997. PubMed ID: 9326319; Reported as as c.2896-1G>T in Table 1, Burwinkel. 1997. PubMed ID: 9215682; PMID: 33858366). RNA studies evidenced that the c.2875-1G>T lead to abnormal splicing (Figure 2, van den Berg. 1997. PubMed ID: 9326319). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-47730291-G-T). Variants that disrupt the consensus splice acceptor site in PHKB are expected to be pathogenic. This variant is interpreted as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003514641 SCV004297724 pathogenic Glycogen storage disease IXb 2024-02-22 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 28 of the PHKB 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 PHKB are known to be pathogenic (PMID: 9215682, 9326319). This variant is present in population databases (rs764133797, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with clinical features of glycogen storage disease type IXb (PMID: 9215682, 9326319). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 2896 –2911. ClinVar contains an entry for this variant (Variation ID: 2637056). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.