Submissions for variant NM_001032.5(RPS29):c.63-6T>G

dbSNP: rs1594573747

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001004902	SCV001164400	uncertain significance	Diamond-Blackfan anemia 13	2018-12-03	criteria provided, single submitter	research	The heterozygous c.63-6T>G variant in RPS29 was identified by our study in one individual with Diamond-Blackfan anemia and their unaffected parent. However, Diamond-Blackfan anemia caused by RPS29 genetic variants is known to show incomplete penetrance and variable expressivity (PMID: 24829207). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. This variant was absent from large populational studies. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. However, RNA-seq of this variant, conducted by our study, showed aberrant splicing and nonsense transcripts. A variant (c.63-3C>A) that is predicted to impact the same splice site has been reported in at least one individual with Diamond-Blackfan anemia in ClinVar and the literature (Variation ID: 449694). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PS3, BP4 (Richards 2015).
CeGaT Center for Human Genetics Tuebingen	RCV002292598	SCV002585469	uncertain significance	not provided	2022-08-01	criteria provided, single submitter	clinical testing	RPS29: PM2, BP4