rs563146441
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_017534.6(MYH2):c.1227C>T(p.Val409Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,614,106 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
MYH2
NM_017534.6 synonymous
NM_017534.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.56
Genes affected
MYH2 (HGNC:7572): (myosin heavy chain 2) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in inclusion body myopathy-3. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Sep 2009]
MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 17-10539483-G-A is Benign according to our data. Variant chr17-10539483-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 321692.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.57 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MYH2 | NM_017534.6 | c.1227C>T | p.Val409Val | synonymous_variant | Exon 13 of 40 | ENST00000245503.10 | NP_060004.3 | |
| MYH2 | NM_001100112.2 | c.1227C>T | p.Val409Val | synonymous_variant | Exon 13 of 40 | NP_001093582.1 | ||
| MYHAS | NR_125367.1 | n.168-28054G>A | intron_variant | Intron 2 of 10 |
Ensembl
Frequencies
GnomAD3 genomes 0.000125 AC: 19AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000239 AC: 60AN: 251404Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135866
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GnomAD4 exome AF: 0.000174 AC: 254AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.000166 AC XY: 121AN XY: 727244
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GnomAD4 genome 0.000125 AC: 19AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74420
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inclusion Body Myopathy, Dominant Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
MYH2-related disorder Benign:1
Nov 04, 2022
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Myopathy, proximal, and ophthalmoplegia Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at