ClinVar Miner

Submissions for variant NM_006420.3(ARFGEF2):c.4790C>T (p.Thr1597Met)

gnomAD frequency: 0.00007  dbSNP: rs368410119
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000430855 SCV000521479 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ARFGEF2 gene. The T1597M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The T1597M variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The T1597M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. This substitution occurs at a position where amino acids with similar properties to Threonine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000430855 SCV002982252 uncertain significance not provided 2023-12-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1597 of the ARFGEF2 protein (p.Thr1597Met). This variant is present in population databases (rs368410119, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ARFGEF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 381815). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002519530 SCV003553585 uncertain significance Inborn genetic diseases 2020-11-23 criteria provided, single submitter clinical testing The c.4790C>T (p.T1597M) alteration is located in exon 36 (coding exon 36) of the ARFGEF2 gene. This alteration results from a C to T substitution at nucleotide position 4790, causing the threonine (T) at amino acid position 1597 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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