rs2233261
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000432.4(MYL2):c.381G>A(p.Ala127=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000938 in 1,614,156 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A127A) has been classified as Likely benign.
Frequency
Consequence
NM_000432.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.381G>A | p.Ala127= | synonymous_variant | 6/7 | ENST00000228841.15 | |
MYL2 | NM_001406745.1 | c.339G>A | p.Ala113= | synonymous_variant | 5/6 | ||
MYL2 | NM_001406916.1 | c.324G>A | p.Ala108= | synonymous_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.381G>A | p.Ala127= | synonymous_variant | 6/7 | 1 | NM_000432.4 | P1 | |
MYL2 | ENST00000548438.1 | c.339G>A | p.Ala113= | synonymous_variant | 5/6 | 3 | |||
MYL2 | ENST00000663220.1 | c.324G>A | p.Ala108= | synonymous_variant | 6/7 | ||||
MYL2 | ENST00000549029.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00509 AC: 775AN: 152144Hom.: 10 Cov.: 33
GnomAD3 exomes AF: 0.00120 AC: 301AN: 251490Hom.: 2 AF XY: 0.000861 AC XY: 117AN XY: 135920
GnomAD4 exome AF: 0.000506 AC: 739AN: 1461894Hom.: 10 Cov.: 33 AF XY: 0.000433 AC XY: 315AN XY: 727248
GnomAD4 genome ? AF: 0.00509 AC: 775AN: 152262Hom.: 10 Cov.: 33 AF XY: 0.00453 AC XY: 337AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 20, 2008 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 07, 2014 | - - |
Hypertrophic cardiomyopathy 10 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 08, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 03, 2015 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Hypertrophic cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Oct 10, 2022 | - - |
Primary familial hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at