rs201255023
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001103.4(ACTN2):c.1975-6C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001103.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACTN2 | NM_001103.4 | c.1975-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000366578.6 | |||
ACTN2 | NM_001278343.2 | c.1975-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
ACTN2 | NR_184402.1 | n.2347-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACTN2 | ENST00000366578.6 | c.1975-6C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001103.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251464Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727232
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74476
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 17, 2014 | The 1975-6C>A variant in ACTN2 has not been previously reported in individuals w ith cardiomyopathy or in large population studies. This variant is located in th e 3' splice region. Computational tools do not suggest an impact to splicing; ho wever, this information is not predictive enough to rule out pathogenicity. Addi tional information is needed to fully assess the clinical significance of the 19 75-6C>A variant. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 23, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Primary familial hypertrophic cardiomyopathy;C2677338:Dilated cardiomyopathy 1AA Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at