rs727503298
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000432.4(MYL2):āc.237T>Cā(p.Phe79Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,100 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 (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Consequence
MYL2
NM_000432.4 synonymous
NM_000432.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.295
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 -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 12-110914223-A-G is Benign according to our data. Variant chr12-110914223-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 164477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.295 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.237T>C | p.Phe79Phe | synonymous_variant | 4/7 | ENST00000228841.15 | NP_000423.2 | |
MYL2 | NM_001406745.1 | c.195T>C | p.Phe65Phe | synonymous_variant | 3/6 | NP_001393674.1 | ||
MYL2 | NM_001406916.1 | c.180T>C | p.Phe60Phe | synonymous_variant | 4/7 | NP_001393845.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.237T>C | p.Phe79Phe | synonymous_variant | 4/7 | 1 | NM_000432.4 | ENSP00000228841.8 | ||
MYL2 | ENST00000548438.1 | c.195T>C | p.Phe65Phe | synonymous_variant | 3/6 | 3 | ENSP00000447154.1 | |||
MYL2 | ENST00000663220.1 | c.180T>C | p.Phe60Phe | synonymous_variant | 4/7 | ENSP00000499568.1 | ||||
MYL2 | ENST00000549029.1 | n.68T>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 12, 2013 | Phe79Phe in exon 4 of MYL2: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. Phe79Phe in exon 4 of MYL2 (allele frequency = n/a) - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at