ClinVar Miner

Submissions for variant NM_001851.5(COL9A1):c.876+2T>A (rs149830493)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579034 SCV000680514 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing The c.876+2 T>A splice site variant has been reported as pathogenic in a 9 year old male who underwent whole exome sequencing and was noted to also harbor a likely pathogenic variant in a different gene (Posey et al., 2017); however, no clinical details were provided and segregation data was unavailable. The c.876+2 T>A variant destroys the canonical splice donor site in intron 8. However, the adjacent exon is predicted to remain in-frame. Therefore, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. Furthermore, no other splice site variants in the COL9A1 gene have been reported in HGMD in association with multiple epiphyseal dysplasia or Stickler syndrome (Stenson et al., 2014). Finally, the c.876+2 T>A variant is observed in 18/126,000 (0.014%) European (non-Finnish) alleles in large population cohorts (Lek et al., 2016).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000579034 SCV001154812 likely pathogenic not provided 2016-06-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000415246 SCV000328817 pathogenic Multiple epiphyseal dysplasia 6 2016-05-01 no assertion criteria provided clinical testing Our laboratory has reported dual molecular diagnoses in COL9A1 (NM_001851.4:c.876+2T>A) and ATRX (NM_000489.3:c.569C>T) in an individual with prematurity with intrauterine growth retardation, profound failure to thrive and global developmental delay, congenital heart disease, visual impairment, severe scoliosis, hypertonia/spasticity, joint contractures, microcephaly, intellectual disability, structural brain abnormality, bowel malrotation and obstruction, short stature, dysmorphic features, cleft uvula, genital anomalies and organomegaly.

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