NM_007255.3(B4GALT7):c.38G>A (p.Trp13Ter) AND Ehlers-Danlos syndrome, spondylodysplastic type, 1

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 13, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002470837.2

Allele description [Variation Report for NM_007255.3(B4GALT7):c.38G>A (p.Trp13Ter)]

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

Genes:

LOC129995400:ATAC-STARR-seq lymphoblastoid silent region 16704 [Gene]
B4GALT7:beta-1,4-galactosyltransferase 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

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

Other names:

p.Trp13*

HGVS:

NC_000005.10:g.177600248G>A
NG_015977.1:g.5131G>A
NG_051237.1:g.13101G>A
NM_007255.3:c.38G>AMANE SELECT
NP_009186.1:p.Trp13Ter
NC_000005.9:g.177027249G>A
NM_007255.2:c.38G>A

Protein change:

W13*

Links:

dbSNP: rs200503833

NCBI 1000 Genomes Browser:

rs200503833

Molecular consequence:

NM_007255.3:c.38G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Ehlers-Danlos syndrome, spondylodysplastic type, 1 (EDSSPD1)
Synonyms:: DERMATAN SULFATE PROTEOGLYCAN; EHLERS-DANLOS SYNDROME, PROGEROID TYPE, 1; GALACTOSYLTRANSFERASE I DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0020682; MedGen: C4552003; OMIM: 130070

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002767923	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 2, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31278392, 31614862, 25741868
SCV004232713	HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - UCC-HudsonAlpha	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 13, 2023)	maternal	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002767923

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 2, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004232713

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - UCC-HudsonAlpha

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 13, 2023)

maternal

research

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	maternal	yes	1	not provided	not provided	1	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expansion of B4GALT7 linkeropathy phenotype to include perinatal lethal skeletal dysplasia.

Mihalic Mosher T, Zygmunt DA, Koboldt DC, Kelly BJ, Johnson LR, McKenna DS, Hood BC, Hickey SE, White P, Wilson RK, Martin PT, McBride KL.

Eur J Hum Genet. 2019 Oct;27(10):1569-1577. doi: 10.1038/s41431-019-0464-8. Epub 2019 Jul 5.

PubMed [citation]

PMID:: 31278392
PMCID:: PMC6777465

Severe Peripheral Joint Laxity is a Distinctive Clinical Feature of Spondylodysplastic-Ehlers-Danlos Syndrome (EDS)-B4GALT7 and Spondylodysplastic-EDS-B3GALT6.

Caraffi SG, Maini I, Ivanovski I, Pollazzon M, Giangiobbe S, Valli M, Rossi A, Sassi S, Faccioli S, Rocco MD, Magnani C, Campos-Xavier B, Unger S, Superti-Furga A, Garavelli L.

Genes (Basel). 2019 Oct 12;10(10). doi: 10.3390/genes10100799.

PubMed [citation]

PMID:: 31614862
PMCID:: PMC6826576

See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767923.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology - UCC-HudsonAlpha, SCV004232713.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Nov 18, 2024

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