ClinVar Miner

Submissions for variant NM_000521.4(HEXB):c.1614-14C>A (rs201448394)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079060 SCV000110929 benign not specified 2012-08-29 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000079060 SCV000304649 benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000079060 SCV000513237 likely benign not specified 2017-02-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl RCV000673104 SCV000798272 likely benign Sandhoff disease 2018-03-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000079060 SCV000919511 benign not specified 2018-12-10 criteria provided, single submitter clinical testing Variant summary: HEXB c.1614-14C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing, which a functional study, Sobek_2012, supports these predictions. The variant allele was found at a frequency of 0.00017 in 277098 control chromosomes (gnomAD and publication). This frequency is not significantly higher than expected for a pathogenic variant in HEXB causing Sandhoff Disease (0.00017 vs 0.0015), allowing no conclusion about variant significance. c.1614-14C>A has been reported in the literature in individuals affected with Sandhoff Disease (Giagnard_2013, Jarnes_2017, Sobek_2012). Although multiple reported affected individuals carried the variant in cis with another pathogenic HEXB variant, in particular, the exon 1-5 deletion, c.-117_669del was reported to be linked with the variant (Sobek_2012). Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000673104 SCV001018425 likely benign Sandhoff disease 2020-12-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000673104 SCV001315842 likely benign Sandhoff disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001310507 SCV001500339 likely benign not provided 2020-07-01 criteria provided, single submitter clinical testing

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