rs397516409
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000432.4(MYL2):c.82G>A(p.Glu28Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E28D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000432.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.82G>A | p.Glu28Lys | missense_variant | 2/7 | ENST00000228841.15 | |
MYL2 | NM_001406745.1 | c.82G>A | p.Glu28Lys | missense_variant | 2/6 | ||
MYL2 | NM_001406916.1 | c.25G>A | p.Glu9Lys | missense_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.82G>A | p.Glu28Lys | missense_variant | 2/7 | 1 | NM_000432.4 | P1 | |
MYL2 | ENST00000548438.1 | c.82G>A | p.Glu28Lys | missense_variant | 2/6 | 3 | |||
MYL2 | ENST00000663220.1 | c.25G>A | p.Glu9Lys | missense_variant | 2/7 | ||||
MYL2 | ENST00000546404.1 | c.82G>A | p.Glu28Lys | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 12, 2012 | Variant classified as Uncertain Significance - Favor Pathogenic. The Glu28Lys va riant in MYL2 has not been reported in the literature nor previously identified in >2300 individuals (>1400 Caucasian) tested by our laboratory. This low freque ncy supports a pathogenic role. Glutamic acid (Glu) at position 28 is highly con served in mammals and across evolutionarily distant species and the change to Ly sine (Lys) was predicted to be pathogenic using a computational tool, which was validated by our laboratory using a set of cardiomyopathy variants with well-est ablished clinical significance. This tool's pathogenic prediction is estimated t o be correct 94% of the time (Jordan 2011). Although this data suggests that the Glu28Lys variant may be pathogenic, additional studies are needed to fully asse ss its clinical significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at