Submissions for variant NM_005262.3(GFER):c.280G>A (p.Asp94Asn)

dbSNP: rs1490540568

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001195755	SCV001366175	uncertain significance	Congenital cataract-progressive muscular hypotonia-hearing loss-developmental delay syndrome	2018-09-27	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355569	SCV001550492	uncertain significance	not provided		no assertion criteria provided	clinical testing	The GFER p.Asp94Asn variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs1490540568) but was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, or the Genome Aggregation Database (March 6, 2019, v2.1.1). The p.Asp94 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; 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. This variant is classified as a variant of uncertain significance.