rs61736461
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_017534.6(MYH2):c.4989G>A(p.Leu1663=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,614,214 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 2 hom. )
Consequence
MYH2
NM_017534.6 synonymous
NM_017534.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.96
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 17-10524652-C-T is Benign according to our data. Variant chr17-10524652-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 284838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.96 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 2 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.4989G>A | p.Leu1663= | synonymous_variant | 35/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-42885C>T | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.4989G>A | p.Leu1663= | synonymous_variant | 35/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.4989G>A | p.Leu1663= | synonymous_variant | 35/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.207-8672C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00348 AC: 529AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000907 AC: 228AN: 251342Hom.: 2 AF XY: 0.000714 AC XY: 97AN XY: 135834
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GnomAD4 exome AF: 0.000305 AC: 446AN: 1461894Hom.: 2 Cov.: 33 AF XY: 0.000275 AC XY: 200AN XY: 727248
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 22, 2015 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2020 | - - |
Myopathy, proximal, and ophthalmoplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
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