Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001354946 | SCV002331061 | likely benign | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003952610 | SCV004770720 | likely benign | KMT2C-related condition | 2022-06-01 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
ITMI | RCV000121528 | SCV000085722 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Department of Pathology and Laboratory Medicine, |
RCV001354946 | SCV001549678 | likely benign | not provided | no assertion criteria provided | clinical testing | The KMT2C p.P4508S variant was not identified in the literature but was identified in dbSNP (ID: rs182572555) and ClinVar (submitted by ITMI, no classification provided). The variant was identified in control databases in 58 of 282632 chromosomes at a frequency of 0.0002052, and was observed at the highest frequency in the Latino population in 53 of 35436 chromosomes (freq: 0.001496) (Genome Aggregation Database March 6, 2019, v2.1.1). This frequency is greater than expected for the rare, autosomal dominant Kleefstra syndrome 2 associated with KMT2C variants. The p.P4508 residue is conserved in mammals and more distantly related organisms however computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |