rs719277
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_017534.6(MYH2):c.904+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,539,660 control chromosomes in the GnomAD database, including 148,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.41 ( 13798 hom., cov: 33)
Exomes 𝑓: 0.43 ( 134908 hom. )
Consequence
MYH2
NM_017534.6 intron
NM_017534.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.929
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 17-10542865-C-T is Benign according to our data. Variant chr17-10542865-C-T is described in ClinVar as [Benign]. Clinvar id is 260829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10542865-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.904+10G>A | intron_variant | ENST00000245503.10 | |||
MYHAS | NR_125367.1 | n.168-24672C>T | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.904+10G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.904+10G>A | intron_variant | 1 | NM_017534.6 | P1 | |||
MYH2 | ENST00000532183.6 | c.904+10G>A | intron_variant | 1 | |||||
MYH2 | ENST00000622564.4 | c.904+10G>A | intron_variant | 1 | |||||
MYH2 | ENST00000397183.6 | c.904+10G>A | intron_variant | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.412 AC: 62530AN: 151876Hom.: 13786 Cov.: 33
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GnomAD3 exomes AF: 0.486 AC: 119756AN: 246534Hom.: 31373 AF XY: 0.485 AC XY: 64730AN XY: 133338
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GnomAD4 exome AF: 0.429 AC: 595951AN: 1387666Hom.: 134908 Cov.: 24 AF XY: 0.434 AC XY: 301360AN XY: 694496
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GnomAD4 genome ? AF: 0.412 AC: 62583AN: 151994Hom.: 13798 Cov.: 33 AF XY: 0.424 AC XY: 31486AN XY: 74284
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2018 | - - |
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