rs112882610
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP3_ModerateBP6BS2
The NM_001103.4(ACTN2):c.920G>A(p.Arg307Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,902 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R307L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001103.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.920G>A | p.Arg307Gln | missense_variant | 10/21 | ENST00000366578.6 | |
ACTN2 | NM_001278343.2 | c.920G>A | p.Arg307Gln | missense_variant | 10/21 | ||
ACTN2 | NR_184402.1 | n.1292G>A | non_coding_transcript_exon_variant | 12/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN2 | ENST00000366578.6 | c.920G>A | p.Arg307Gln | missense_variant | 10/21 | 1 | NM_001103.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152014Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251454Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135904
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461888Hom.: 0 Cov.: 67 AF XY: 0.0000220 AC XY: 16AN XY: 727246
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152014Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74238
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2022 | The p.R307Q variant (also known as c.920G>A), located in coding exon 10 of the ACTN2 gene, results from a G to A substitution at nucleotide position 920. The arginine at codon 307 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in an individual from a dilated cardiomyopathy cohort; however, details were limited (Mazzarotto F et al. Circulation. 2020 02;141(5):387-398). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Primary familial hypertrophic cardiomyopathy;C2677338:Dilated cardiomyopathy 1AA Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at