ClinVar Miner

Submissions for variant NM_080679.2(COL11A2):c.798+1585G>A (rs139116571)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724260 SCV000232326 uncertain significance not provided 2014-10-08 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000223442 SCV000271609 uncertain significance not specified 2015-06-22 criteria provided, single submitter clinical testing The p.Gly297Ser variant in COL11A2 has not been previously reported in individua ls with hearing loss, but has been identified in 1/6758 European American chromo somes by the NHLBI Exome sequencing project (; dbSNP rs139116571). Computational prediction tools and conservation analyses su ggest that the p.Gly297Ser variant may not impact the protein, though this infor mation is not predictive enough to rule out pathogenicity. In summary, the clini cal significance of the p.Gly297Ser variant is uncertain.
GeneDx RCV000724260 SCV000491063 uncertain significance not provided 2018-06-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL11A2 gene. Although the G297S variant has not been published as pathogenic or been reported as benign to our knowledge, it has been identified in conjunction with other cardiogenetic variants in two other unrelated individuals referred to GeneDx for connective tissue disorder genetic testing. This variant is observed in 16/72,228 alleles (0.02%) from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016). The G297S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678342 SCV000804406 uncertain significance Otospondylomegaepiphyseal dysplasia, autosomal dominant 2017-10-03 criteria provided, single submitter provider interpretation This 9 year old female has severe intellectual disability, growth and feeding problems requiring a G-tube as an infant, a repaired cleft palate, short stature (4 SD below average), microcephaly, scoliosis, deviated septum, widely set nipples, curved 4th and 5th digits bilaterally, recurrent nosebleeds, and possible hearing loss. Dysmorphic facial features include midface depression, prominent forehead, low set and posteriorly rotated ears, and micrognathia. Benign pulmonary artery branch stenosis and a small PFO were noted on echocardiogram, and an abnormal brain MRI done at 8 years of age showed scattered, non-enhancing, non-specific punctate predominately subcortical T2 hyperintensities with mild-moderate cerebral volume loss. Her bone age at 8 years, 1 month was essentially normal (0.3 SD below mean). Tympanograms were done at 7 years of age and were within normal limits bilaterally with OAEs at fail/refer results bilaterally. The p.G297S variant was maternally inherited and is present in gnomAD, occurring 0.01% in the Latino population and 0.02% in European non-Finnish. Computational model predictions are inconsistent. A second VUS was also identified in COLL11A2, inheritance is unknown.
Fulgent Genetics,Fulgent Genetics RCV000764647 SCV000895756 uncertain significance Deafness, autosomal recessive 53; Deafness, autosomal dominant 13; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Otospondylomegaepiphyseal dysplasia, autosomal dominant; Fibrochondrogenesis 2 2018-10-31 criteria provided, single submitter clinical testing

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