ClinVar Miner

Submissions for variant NM_001613.4(ACTA2):c.78C>A (p.Asp26Glu)

dbSNP: rs141538225
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000703601 SCV000832509 uncertain significance Aortic aneurysm, familial thoracic 6 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 26 of the ACTA2 protein (p.Asp26Glu). This variant is present in population databases (rs141538225, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ACTA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 580143). 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 ACTA2 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.
Color Diagnostics, LLC DBA Color Health RCV001524997 SCV001734983 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-09 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 26 of the ACTA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 17/251074 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002507232 SCV002816729 uncertain significance Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction syndrome; Moyamoya disease 5 2021-09-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV001524997 SCV003740151 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-04-22 criteria provided, single submitter clinical testing The c.78C>A (p.D26E) alteration is located in exon 2 (coding exon 1) of the ACTA2 gene. This alteration results from a C to A substitution at nucleotide position 78, causing the aspartic acid (D) at amino acid position 26 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV001524997 SCV004840672 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-08-29 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glutamic acid at codon 26 of the ACTA2 protein. Computational prediction tools indicate that this variant's impact on protein structure and function is inconclusive. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ACTA2-related disorders in the literature. This variant has been identified in 17/251074 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The elevated variant allele frequency in the general population indicates that this variant may not be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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