chr10-88935264-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_001613.4(ACTA2):c.1093G>A(p.Asp365Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D365E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001613.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTA2 | NM_001613.4 | c.1093G>A | p.Asp365Asn | missense_variant | 9/9 | ENST00000224784.10 | |
ACTA2-AS1 | NR_125373.1 | n.889C>T | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTA2 | ENST00000224784.10 | c.1093G>A | p.Asp365Asn | missense_variant | 9/9 | 1 | NM_001613.4 | P1 | |
ACTA2-AS1 | ENST00000437930.4 | n.930C>T | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251244Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135772
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461616Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727108
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Sep 17, 2023 | This missense variant replaces aspartic acid with asparagine at codon 365 of the ACTA2 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 ACTA2-related disorders in the literature. This variant has been identified in 2/251244 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at