ClinVar Miner

Submissions for variant NM_207122.2(EXT2):c.1588G>A (p.Glu530Lys)

gnomAD frequency: 0.00079  dbSNP: rs148711133
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000250542 SCV000317230 likely benign not specified criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000726040 SCV000341407 uncertain significance not provided 2016-05-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001081789 SCV001106710 likely benign Exostoses, multiple, type 2 2025-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002518674 SCV003528755 uncertain significance Inborn genetic diseases 2021-08-30 criteria provided, single submitter clinical testing The c.1588G>A (p.E530K) alteration is located in exon 10 (coding exon 9) of the EXT2 gene. This alteration results from a G to A substitution at nucleotide position 1588, causing the glutamic acid (E) at amino acid position 530 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000726040 SCV001550752 likely benign not provided no assertion criteria provided clinical testing The EXT2 p.E563K variant was identified in 1 individual with Müllerian adenosarcoma (Howitt_2015_PMID:25231023). The variant was identified in dbSNP (ID: rs148711133) and ClinVar (classified as likely benign by Prevention Genetics and Invitae; and as uncertain significance by EGL Genetic Diagnostics). This variant was not found in COSMIC. The variant was identified in control databases in 166 of 282838 chromosomes (1 homozygous) at a frequency of 0.0005869, and was observed at the highest frequency in the European (non-Finnish) population in 148 of 129156 chromosomes (freq: 0.001146) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.E563 residue is conserved in mammals and 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.

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