Submissions for variant NM_014140.4(SMARCAL1):c.2644_2646del (p.Ile882del)

gnomAD frequency: 0.00002  dbSNP: rs1315596315

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001369967	SCV001566426	uncertain significance	Schimke immuno-osseous dysplasia	2022-02-05	criteria provided, single submitter	clinical testing	This variant, c.2644_2646del, results in the deletion of 1 amino acid(s) of the SMARCAL1 protein (p.Ile882del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SMARCAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1060525). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001369967	SCV003924247	uncertain significance	Schimke immuno-osseous dysplasia	2022-10-28	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.004% (3/68036) (https://gnomad.broadinstitute.org/variant/2-216482755-GATC-G?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:1060525). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 1 amino acid at position 882 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In addition, although this variant occurs in the exon, splice prediction tools suggest that this variant may impact splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Natera, Inc.	RCV001369967	SCV002076337	uncertain significance	Schimke immuno-osseous dysplasia	2020-03-21	no assertion criteria provided	clinical testing