Submissions for variant NM_000399.5(EGR2):c.665T>C (p.Met222Thr)

gnomAD frequency: 0.00004  dbSNP: rs530614586

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000734025	SCV000862136	uncertain significance	not provided	2018-06-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079407	SCV001011357	benign	Charcot-Marie-Tooth disease, type I	2024-10-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000734025	SCV002107206	uncertain significance	not provided	2022-03-03	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002360861	SCV002666368	uncertain significance	Inborn genetic diseases	2021-06-09	criteria provided, single submitter	clinical testing	The p.M222T variant (also known as c.665T>C), located in coding exon 2 of the EGR2 gene, results from a T to C substitution at nucleotide position 665. The methionine at codon 222 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000734025	SCV003831840	uncertain significance	not provided	2022-08-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004800565	SCV005422780	uncertain significance	not specified	2024-10-17	criteria provided, single submitter	clinical testing	Variant summary: EGR2 c.665T>C (p.Met222Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251494 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.665T>C in individuals affected with EGR2-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 597793). Based on the evidence outlined above, the variant was classified as uncertain significance.