rs397516405
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000432.4(MYL2):c.447C>T(p.Asn149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,464 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 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
MYL2
NM_000432.4 synonymous
NM_000432.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 12-110911131-G-A is Benign according to our data. Variant chr12-110911131-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 43477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.74 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.447C>T | p.Asn149= | synonymous_variant | 7/7 | ENST00000228841.15 | |
MYL2 | NM_001406745.1 | c.405C>T | p.Asn135= | synonymous_variant | 6/6 | ||
MYL2 | NM_001406916.1 | c.390C>T | p.Asn130= | synonymous_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.447C>T | p.Asn149= | synonymous_variant | 7/7 | 1 | NM_000432.4 | P1 | |
MYL2 | ENST00000548438.1 | c.405C>T | p.Asn135= | synonymous_variant | 6/6 | 3 | |||
MYL2 | ENST00000663220.1 | c.390C>T | p.Asn130= | synonymous_variant | 7/7 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151948Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461516Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727044
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151948Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74196
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
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 | Jul 06, 2012 | Asn149Asn in exon 7 of MYL2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. Asn149Asn in exon 7 of MYL2 (allele frequency = n/a) - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 23, 2021 | - - |
Hypertrophic cardiomyopathy 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 18, 2023 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 04, 2023 | - - |
Computational scores
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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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at