ClinVar Miner

Submissions for variant NM_005236.3(ERCC4):c.257G>A (p.Arg86His)

gnomAD frequency: 0.00006  dbSNP: rs187435008
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802175 SCV000941993 uncertain significance Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q 2023-11-22 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 86 of the ERCC4 protein (p.Arg86His). This variant is present in population databases (rs187435008, gnomAD 0.06%). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 32487094). ClinVar contains an entry for this variant (Variation ID: 647625). 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 not expected to disrupt ERCC4 protein function with a negative 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.
Baylor Genetics RCV001788354 SCV002030161 uncertain significance Fanconi anemia complementation group Q 2021-08-24 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002537142 SCV003590131 uncertain significance Inborn genetic diseases 2021-11-24 criteria provided, single submitter clinical testing The c.257G>A (p.R86H) alteration is located in exon 2 (coding exon 2) of the ERCC4 gene. This alteration results from a G to A substitution at nucleotide position 257, causing the arginine (R) at amino acid position 86 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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