ClinVar Miner

Submissions for variant NM_001478.5(B4GALNT1):c.263dup (p.Leu89fs)

dbSNP: rs745744124
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622734 SCV000742302 pathogenic Inborn genetic diseases 2017-03-14 criteria provided, single submitter clinical testing
GeneDx RCV001009218 SCV001169037 likely pathogenic not provided 2019-03-15 criteria provided, single submitter clinical testing The c.263dupG variant in the B4GALNT1 gene has been reported previously in the homozygous state in an individual with hereditary spastic paraplegia with learning disability, lower limb spasticity and weakness, nystagmus, axonal sensitive neuropathy, white matter hyperintensities, and cerebral atrophy (Boukhris et al., 2013). The c.263dupG variant causes a frameshift starting with codon Leucine 89, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Leu89ProfsX13. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.263dupG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.263dupG as a likely pathogenic variant.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000054421 SCV001448891 pathogenic Hereditary spastic paraplegia 26 2019-02-22 criteria provided, single submitter clinical testing
Genomics England Pilot Project, Genomics England RCV000054421 SCV001760310 pathogenic Hereditary spastic paraplegia 26 criteria provided, single submitter clinical testing
Invitae RCV002515735 SCV003288334 pathogenic Spastic paraplegia 2023-03-07 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 60525). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 23746551, 32214227). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Leu89Profs*13) in the B4GALNT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in B4GALNT1 are known to be pathogenic (PMID: 23746551).
Baylor Genetics RCV000054421 SCV004183453 pathogenic Hereditary spastic paraplegia 26 2023-10-27 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001009218 SCV004227285 pathogenic not provided 2022-05-31 criteria provided, single submitter clinical testing PM2, PM3, PS3, PVS1
OMIM RCV000054421 SCV000082898 pathogenic Hereditary spastic paraplegia 26 2013-07-11 no assertion criteria provided literature only
Section for Clinical Neurogenetics, University of Tübingen RCV000054421 SCV001156080 likely pathogenic Hereditary spastic paraplegia 26 2019-08-01 no assertion criteria provided research

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