Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005407009 | SCV006072414 | uncertain significance | not specified | 2025-03-05 | criteria provided, single submitter | clinical testing | Variant summary: B4GALT7 c.38G>A (p.Trp13X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, however current evidence is not sufficient to establish loss of function as a mechanism for disease. The variant allele was found at a frequency of 0.00021 in 62262 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in B4GALT7 causing Spondylodysplastic Ehlers-Danlos syndrome (0.00021 vs 0.0011), allowing no conclusion about variant significance. c.38G>A has been reported in the literature in individuals affected with cardiovascular disease or spontaneous coronary artery dissection and/or an unspecified connective tissue disorder, both without reported second variant and without evidence of causality (e.g. Glicksberg_2019, Tarr_2022). These report(s) do not provide unequivocal conclusions about association of the variant with Spondylodysplastic Ehlers-Danlos syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 282261). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Department of Pathology and Laboratory Medicine, |
RCV002470837 | SCV005918305 | uncertain significance | Ehlers-Danlos syndrome, spondylodysplastic type, 1 | 2023-10-02 | criteria provided, single submitter | research | |
| Hudson |
RCV002470837 | SCV004232713 | likely pathogenic | Ehlers-Danlos syndrome, spondylodysplastic type, 1 | 2023-11-13 | criteria provided, single submitter | research | |
| Mayo Clinic Laboratories, |
RCV000725058 | SCV004227161 | uncertain significance | not provided | 2023-06-22 | criteria provided, single submitter | clinical testing | PVS1 |
| Victorian Clinical Genetics Services, |
RCV002470837 | SCV002767923 | pathogenic | Ehlers-Danlos syndrome, spondylodysplastic type, 1 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Ehlers-Danlos syndrome, spondylodysplastic type, 1 (MIM#130070) (PMID: 31278392). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v3) <0.01 for a recessive condition (39 heterozygotes, 0 homozygotes). (SP) 0703 - Other NMD-predicted variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. These two variants have been reported as likely pathogenic, and have been reported in several patients with spondodylodysplastic-Ehlers-Danlos syndrome (EDS) (PMID: 31614862, ClinVar, Decipher). (SP) 0808 - Previous reports of pathogenicity for this variant are conflicting. This variant has been reported as both likely pathogenic and as a VUS (ClinVar and NTD Genetics). It has also been observed as homozygous in an individual with global developmental delay, broad-based gait and stereotypy, but subsequently classified as benign with no other information provided (DECIPHER). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Genome Diagnostics Laboratory, |
RCV002278270 | SCV002565306 | uncertain significance | Ehlers-Danlos syndrome | 2019-12-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000725058 | SCV002028256 | pathogenic | not provided | 2024-11-11 | criteria provided, single submitter | clinical testing | Has not been previously reported in association with a B4GALT7-related disorder to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31345219) |
| Labcorp Genetics |
RCV000344285 | SCV000766704 | uncertain significance | Ehlers-Danlos syndrome progeroid type | 2022-08-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp13*) in the B4GALT7 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in B4GALT7 cause disease. This variant is present in population databases (rs200503833, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with B4GALT7-related conditions. ClinVar contains an entry for this variant (Variation ID: 282261). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Eurofins Ntd Llc |
RCV000725058 | SCV000333628 | likely pathogenic | not provided | 2015-08-14 | criteria provided, single submitter | clinical testing |