Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001357478 | SCV004553923 | likely benign | not provided | 2023-10-14 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001357478 | SCV001552960 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The ASXL2 p.Gly5Arg variant was not identified in the ClinVar, Cosmic or MutDB databases. The variant was identified in dbSNP (ID: rs371056638), LOVD 3.0 and in control databases in 30 of 280406 chromosomes at a frequency of 0.000107 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 28 of 128260 chromosomes (freq: 0.000218), African in 1 of 24192 chromosomes (freq: 0.000041) and European (Finnish) in 1 of 24960 chromosomes (freq: 0.00004); it was not observed in the Latino, Ashkenazi Jewish, East Asian, Other, and South Asian populations. Lasho et al. (2018) identified the p.Gly5Arg variant in an individual with myelodysplastic/myeloproliferative neoplasms (Lasho_2018_PMID: 29531217). The p.Gly5 residue is conserved in mammals but not in more distantly related organisms and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |