ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.2550_2554del (p.Lys850fs)

dbSNP: rs281864996
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS RCV000449538 SCV000537770 likely pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2016-01-01 criteria provided, single submitter research
Counsyl RCV000449538 SCV000794572 likely pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2017-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000032320 SCV001362263 likely pathogenic Mucolipidosis type II 2019-11-22 criteria provided, single submitter clinical testing Variant summary: GNPTAB c.2550_2554delGAAAA (p.Lys850AsnfsX10) 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, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.8e-05 in 251182 control chromosomes (gnomAD). c.2550_2554delGAAAA has been reported in the literature in homozygous and compound heterozygous individuals affected with Mucolipidosis type 2 (Liu_2016, Tappino_2009). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV000449538 SCV001581553 pathogenic Mucolipidosis type II; Pseudo-Hurler polydystrophy 2023-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys850Asnfs*10) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). This variant is present in population databases (rs281864996, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with mucolipidosis type II alpha/beta (PMID: 19634183). ClinVar contains an entry for this variant (Variation ID: 39055). For these reasons, this variant has been classified as Pathogenic.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000032320 SCV003915852 pathogenic Mucolipidosis type II 2023-04-13 criteria provided, single submitter clinical testing A heterozygous variation in exon 13 of the GNPTAB gene detected. The observed variant c.2550_2554del has not been reported in the 1000 genomes and MAF 0.0028% in the gnomAD databases. The in silico prediction of the variant are possibly damaging by PolyPhen-2 and damaging by SIFT and MutationTaster. In summary, the variant meets our criteria to be classified as pathogenic.
GeneReviews RCV000032320 SCV000055964 not provided Mucolipidosis type II no assertion provided literature only

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