rs116419997
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Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_017534.6(MYH2):āc.1068G>Cā(p.Thr356Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. 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: š 0.0022 ( 1 hom., cov: 32)
Exomes š: 0.00022 ( 0 hom. )
Consequence
MYH2
NM_017534.6 synonymous
NM_017534.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.615
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.31).
BP6
Variant 17-10540007-C-G is Benign according to our data. Variant chr17-10540007-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 465918.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.1068G>C | p.Thr356Thr | synonymous_variant | 12/40 | ENST00000245503.10 | NP_060004.3 | |
MYH2 | NM_001100112.2 | c.1068G>C | p.Thr356Thr | synonymous_variant | 12/40 | NP_001093582.1 | ||
MYHAS | NR_125367.1 | n.168-27530C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.1068G>C | p.Thr356Thr | synonymous_variant | 12/40 | 1 | NM_017534.6 | ENSP00000245503.5 |
Frequencies
GnomAD3 genomes AF: 0.00214 AC: 326AN: 152072Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000577 AC: 145AN: 251386Hom.: 0 AF XY: 0.000449 AC XY: 61AN XY: 135858
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GnomAD4 exome AF: 0.000215 AC: 315AN: 1461838Hom.: 0 Cov.: 32 AF XY: 0.000190 AC XY: 138AN XY: 727222
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GnomAD4 genome AF: 0.00216 AC: 329AN: 152190Hom.: 1 Cov.: 32 AF XY: 0.00214 AC XY: 159AN XY: 74394
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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
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 10, 2021 | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | MYH2: BP4, BP7 - |
Myopathy, proximal, and ophthalmoplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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