ClinVar Miner

Submissions for variant NM_005670.4(EPM2A):c.680C>T (p.Ala227Val) (rs147399860)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000177234 SCV000229076 uncertain significance not provided 2015-05-05 criteria provided, single submitter clinical testing
GeneDx RCV000177234 SCV000240967 likely benign not provided 2020-12-04 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000177234 SCV000280892 likely benign not provided 2016-01-21 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Invitae RCV001083180 SCV000288975 likely benign Progressive myoclonic epilepsy 2020-11-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000718135 SCV000848997 likely benign Seizures 2019-01-28 criteria provided, single submitter clinical testing In silico models in agreement (benign) ;Other data supporting benign classification
Athena Diagnostics Inc RCV000177234 SCV001143867 likely benign not provided 2019-04-10 criteria provided, single submitter clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252481 SCV001428238 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000177234 SCV001552556 likely benign not provided no assertion criteria provided clinical testing The EPM2A p.Ala227Val variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs147399860) and ClinVar (classified as uncertain significance by EGL Genetics, Ambry Genetics and Invitae, and as likely benign by GeneDx and Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics). The variant was identified in control databases in 317 of 282824 chromosomes (2 homozygous) at a frequency of 0.001121 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Other in 13 of 7222 chromosomes (freq: 0.0018), European (non-Finnish) in 224 of 129136 chromosomes (freq: 0.001735), Latino in 52 of 35438 chromosomes (freq: 0.001467), Ashkenazi Jewish in 9 of 10368 chromosomes (freq: 0.000868), South Asian in 11 of 30616 chromosomes (freq: 0.000359), African in 4 of 24966 chromosomes (freq: 0.00016) and European (Finnish) in 4 of 25124 chromosomes (freq: 0.000159), but was not observed in the East Asian population. The p.Ala227 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.