chr12-110914177-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000432.4(MYL2):c.274+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,599,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000432.4 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.274+9G>A | intron_variant | Intron 4 of 6 | ENST00000228841.15 | NP_000423.2 | ||
MYL2 | NM_001406745.1 | c.232+9G>A | intron_variant | Intron 3 of 5 | NP_001393674.1 | |||
MYL2 | NM_001406916.1 | c.217+9G>A | intron_variant | Intron 4 of 6 | NP_001393845.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.274+9G>A | intron_variant | Intron 4 of 6 | 1 | NM_000432.4 | ENSP00000228841.8 | |||
MYL2 | ENST00000548438.1 | c.232+9G>A | intron_variant | Intron 3 of 5 | 3 | ENSP00000447154.1 | ||||
MYL2 | ENST00000663220.1 | c.217+9G>A | intron_variant | Intron 4 of 6 | ENSP00000499568.1 | |||||
MYL2 | ENST00000549029.1 | n.105+9G>A | intron_variant | Intron 1 of 1 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000855 AC: 13AN: 151980Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251454Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135904
GnomAD4 exome AF: 0.0000414 AC: 60AN: 1447608Hom.: 0 Cov.: 30 AF XY: 0.0000361 AC XY: 26AN XY: 721220
GnomAD4 genome AF: 0.0000855 AC: 13AN: 151980Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74246
ClinVar
Submissions by phenotype
not specified Benign:2
- -
Variant summary: MYL2 c.274+9G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.4e-05 in 251454 control chromosomes. The observed variant frequency is approximately 1.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYL2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.274+9G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. -
Cardiomyopathy Uncertain:1
- -
Hypertrophic cardiomyopathy Uncertain:1
- -
Hypertrophic cardiomyopathy 10 Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at