chr1-236737124-C-G
Variant summary
Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2
The NM_001103.4(ACTN2):c.786C>G(p.Ala262Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,597,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A262A) has been classified as Likely benign.
Frequency
Consequence
NM_001103.4 splice_region, synonymous
Scores
Clinical Significance
Conservation
Publications
- intrinsic cardiomyopathyInheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Laboratory for Molecular Medicine, ClinGen
- myopathy, congenital, with structured cores and z-line abnormalitiesInheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- dilated cardiomyopathy 1AAInheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- heart conduction diseaseInheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
- myopathy, distal, 6, adult-onset, autosomal dominantInheritance: AD, Unknown Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Benign. The variant received -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.786C>G | p.Ala262Ala | splice_region_variant, synonymous_variant | Exon 9 of 21 | ENST00000366578.6 | NP_001094.1 | |
ACTN2 | NM_001278343.2 | c.786C>G | p.Ala262Ala | splice_region_variant, synonymous_variant | Exon 9 of 21 | NP_001265272.1 | ||
ACTN2 | NR_184402.1 | n.1158C>G | splice_region_variant, non_coding_transcript_exon_variant | Exon 11 of 23 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000332 AC: 5AN: 150802Hom.: 0 Cov.: 28 show subpopulations
GnomAD2 exomes AF: 0.0000915 AC: 23AN: 251280 AF XY: 0.0000663 show subpopulations
GnomAD4 exome AF: 0.0000325 AC: 47AN: 1446632Hom.: 0 Cov.: 31 AF XY: 0.0000306 AC XY: 22AN XY: 719680 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000331 AC: 5AN: 150918Hom.: 0 Cov.: 28 AF XY: 0.0000543 AC XY: 4AN XY: 73636 show subpopulations
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at