ClinVar Miner

Submissions for variant NM_001277269.1(OTOG):c.7729+1G>A (rs548496846)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727025 SCV000680945 uncertain significance not provided 2018-08-28 criteria provided, single submitter clinical testing The c.7729+1 G>A splice site variant destroys the canonical splice donor site in intron 45. It is predicted to cause abnormal gene splicing; however, the adjacent exon 45 remains in-frame. In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. The variant is observed in 101/60880 (0.166%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727025 SCV000705006 uncertain significance not provided 2017-01-25 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000578688 SCV000711746 uncertain significance not specified 2018-03-06 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The c.7729+1G>A variant in OTOG has been reported in the heterozygous state in one individual w ith hearing loss (Baux 2017) and has been identified by our laboratory in the he terozygous state in 2 individuals with hearing loss, both of whom had pathogenic variants in other genes sufficient to explain their hearing loss. This variant has also been identified in 0.2% (101/60880) of European chromosomes by the Geno me Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs5484 96846). Although this variant has been seen in the general population, its frequ ency is not high enough to rule out a pathogenic role. This variant occurs in th e invariant region (+/- 1,2) of the splice consensus sequence of exon 45; howeve r, exon 45 is in-frame and it is unclear if altered splicing will lead to an in- frame deletion of exon 45 or an absent protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of the c.7729+1G>A va riant is uncertain. ACMG/AMP Criteria applied: PVS1_Moderate.
Fulgent Genetics,Fulgent Genetics RCV000763724 SCV000894608 uncertain significance Deafness, autosomal recessive 18b 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000727025 SCV001245639 uncertain significance not provided 2019-12-01 criteria provided, single submitter clinical testing

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