Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586364 | SCV000699954 | pathogenic | Sanfilippo syndrome | 2016-08-18 | criteria provided, single submitter | clinical testing | Variant summary: The HGSNAT c.372-2A>G variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict loss of a canonical splicing acceptor site. ESEfinder predicts gain of binding motif for RNA splicing enhancer SRp40. This variant was found in 2/89484 control chromosomes at a frequency of 0.0000224, which does not exceed the estimated maximal expected allele frequency of a pathogenic HGSNAT variant (0.001). This variant has been reported in multiple MPSIIIC patients both as homozygotes and compound heterozygotes. Functional studies showed that this variant cause aberrant splicing and significantly decreased enzyme activity. In addition, multiple reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Invitae | RCV001067306 | SCV001232360 | pathogenic | Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 3 of the HGSNAT 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 HGSNAT are known to be pathogenic (PMID: 17033958, 19479962). This variant is present in population databases (rs483352896, gnomAD 0.02%). Disruption of this splice site has been observed in individual(s) with mucopolysaccharidosis type III/Sanfilippo syndrome (PMID: 18518886, 20825431). ClinVar contains an entry for this variant (Variation ID: 1236). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 18518886, 20825431). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV001067306 | SCV002814956 | pathogenic | Mucopolysaccharidosis, MPS-III-C; Retinitis pigmentosa 73 | 2022-03-21 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000001295 | SCV000021445 | pathogenic | Mucopolysaccharidosis, MPS-III-C | 2011-10-01 | no assertion criteria provided | literature only | |
Counsyl | RCV000001295 | SCV000792528 | pathogenic | Mucopolysaccharidosis, MPS-III-C | 2017-06-29 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000001295 | SCV001460466 | pathogenic | Mucopolysaccharidosis, MPS-III-C | 2020-09-16 | no assertion criteria provided | clinical testing |