ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.-127G>C (rs727503068)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150736 SCV000198172 uncertain significance not specified 2014-07-16 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The -127G>C variant in GJB2 has previously been identified by our laboratory in two individuals wit h hearing loss. However, a second GJB2 variant was not found in either of them. This variant is located in the 5?untranslated region (5'UTR), and variants in th is region could have an effect on transcriptional or translational regulation. H owever, no pathogenic variants have been reported in the 5?UTR of GJB2. In summa ry, although the clinical significance of this variant cannot be determined with certainty at this time, we would lean towards a more likely benign role.
Integrated Genetics/Laboratory Corporation of America RCV000150736 SCV001361876 uncertain significance not specified 2019-05-01 criteria provided, single submitter clinical testing Variant summary: GJB2 c.-127G>C is located in the untranslated mRNA region upstream of the initiation codon. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00022 in 31242 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-127G>C in individuals affected with Autosomal Recessive Non-Syndromic Hearing Loss and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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