Submissions for variant NM_000187.4(HGD):c.87+1G>A

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003336655	SCV004100374	likely pathogenic	Alkaptonuria		criteria provided, single submitter	clinical testing	The splice donor variant c.87+1G>A in HGD (NM_000187.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.87+1G>A variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant affects an invariant splice nucleotide and hence is predicted to cause protein truncation. For these reasons, this variant has been classified as Likely Pathogenic.
Invitae	RCV003336655	SCV004293143	pathogenic	Alkaptonuria	2023-07-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change affects a donor splice site in intron 2 of the HGD 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 HGD are known to be pathogenic (PMID: 12501223, 19862842). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Alkaptonuria (PMID: 24575791). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences	RCV003336655	SCV004046732	pathogenic	Alkaptonuria		no assertion criteria provided	research	The variant was originally described in PMID:24575791. It has been submitted to the HGD gene mutation database (http://hgddatabase.cvtisr.sk/, DB-ID: AKU_00150).