Submissions for variant NM_007255.3(B4GALT7):c.38G>A (p.Trp13Ter)

gnomAD frequency: 0.00019  dbSNP: rs200503833

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725058	SCV000333628	likely pathogenic	not provided	2015-08-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	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.
GeneDx	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)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278270	SCV002565306	uncertain significance	Ehlers-Danlos syndrome	2019-12-01	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	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
Mayo Clinic Laboratories, Mayo Clinic	RCV000725058	SCV004227161	uncertain significance	not provided	2023-06-22	criteria provided, single submitter	clinical testing	PVS1
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV002470837	SCV004232713	likely pathogenic	Ehlers-Danlos syndrome, spondylodysplastic type, 1	2023-11-13	criteria provided, single submitter	research