ClinVar Miner

Submissions for variant NM_005228.5(EGFR):c.2885G>A (p.Arg962His)

gnomAD frequency: 0.00009  dbSNP: rs144496976
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709017 SCV000838218 likely benign Hereditary cancer 2024-04-09 criteria provided, single submitter clinical testing
Invitae RCV001054589 SCV001218932 uncertain significance EGFR-related lung cancer 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 962 of the EGFR protein (p.Arg962His). This variant is present in population databases (rs144496976, gnomAD 0.07%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with breast cancer, osteosarcoma, non-Hodgkin lymphoma, and nodular sclerosis Hodgkin lymphoma (PMID: 32191290, 34308104, 35264596). ClinVar contains an entry for this variant (Variation ID: 134027). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EGFR protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV003975068 SCV004788798 uncertain significance EGFR-related condition 2023-12-19 criteria provided, single submitter clinical testing The EGFR c.2885G>A variant is predicted to result in the amino acid substitution p.Arg962His. This variant has been reported in multiple individuals with breast cancer, osteosarcoma, and diffuse large B cell lymphoma (see for example, Table S3, Guindalini et al. 2022. PubMed ID: 35264596; Table S5, Mirabello et al. 2020. PubMed ID: 32191290; search 55268045 in Table S2, Kim et al. 2021. PubMed ID: 34308104). This variant is reported in 0.065% of alleles in individuals of South Asian descent in gnomAD. This variant has been classified as a variant of uncertain significance by other institutions in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/134027/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
ITMI RCV000120696 SCV000084857 not provided not specified 2013-09-19 no assertion provided reference population

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