12-110913320-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_000432.4(MYL2):c.279G>A(p.Ala93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,614,188 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
MYL2
NM_000432.4 synonymous
NM_000432.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.54
Genes affected
MYL2 (HGNC:7583): (myosin light chain 2) This gene encodes a major sarcomeric protein in mammalian striated muscle. The encoded protein plays a role in embryonic heart muscle structure and function, while phosphorylation of the encoded protein is involved in cardiac myosin cycling kinetics, torsion and function in adults. Mutations in this gene are associated with hypertrophic cardiomyopathy 10 and infant-onset myopathy. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant 12-110913320-C-T is Benign according to our data. Variant chr12-110913320-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 138399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-110913320-C-T is described in Lovd as [Benign].
BS2
?
High AC in GnomAd at 184 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.279G>A | p.Ala93= | synonymous_variant | 5/7 | ENST00000228841.15 | |
MYL2 | NM_001406745.1 | c.237G>A | p.Ala79= | synonymous_variant | 4/6 | ||
MYL2 | NM_001406916.1 | c.222G>A | p.Ala74= | synonymous_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.279G>A | p.Ala93= | synonymous_variant | 5/7 | 1 | NM_000432.4 | P1 | |
MYL2 | ENST00000548438.1 | c.237G>A | p.Ala79= | synonymous_variant | 4/6 | 3 | |||
MYL2 | ENST00000663220.1 | c.222G>A | p.Ala74= | synonymous_variant | 5/7 | ||||
MYL2 | ENST00000549029.1 | n.110G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00121 AC: 184AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000262 AC: 66AN: 251484Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135914
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GnomAD4 exome AF: 0.000153 AC: 224AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.000125 AC XY: 91AN XY: 727242
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 31, 2015 | p.Ala93Ala in exon 5 of MYL2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.4% (40/10404) of A frican chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi nstitute.org; dbSNP rs28645088). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 19, 2013 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 28, 2021 | - - |
Hypertrophic cardiomyopathy 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Sep 21, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jan 20, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 27, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2015 | This alteration is classified as likely 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:
Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at