rs141134519
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_017534.6(MYH2):c.1161G>A(p.Ala387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,613,820 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 Benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 1 hom. )
Consequence
MYH2
NM_017534.6 synonymous
NM_017534.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.49
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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 17-10539549-C-T is Benign according to our data. Variant chr17-10539549-C-T is described in ClinVar as [Benign]. Clinvar id is 465920.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.49 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.1161G>A | p.Ala387= | synonymous_variant | 13/40 | ENST00000245503.10 | NP_060004.3 | |
MYHAS | NR_125367.1 | n.168-27988C>T | intron_variant, non_coding_transcript_variant | |||||
MYH2 | NM_001100112.2 | c.1161G>A | p.Ala387= | synonymous_variant | 13/40 | NP_001093582.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.1161G>A | p.Ala387= | synonymous_variant | 13/40 | 1 | NM_017534.6 | ENSP00000245503 | P1 | |
MYH2 | ENST00000532183.6 | c.1161G>A | p.Ala387= | synonymous_variant | 12/17 | 1 | ENSP00000433944 | |||
MYH2 | ENST00000622564.4 | c.1161G>A | p.Ala387= | synonymous_variant | 13/18 | 1 | ENSP00000482463 | |||
MYH2 | ENST00000397183.6 | c.1161G>A | p.Ala387= | synonymous_variant | 13/40 | 5 | ENSP00000380367 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 151992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000474 AC: 119AN: 251314Hom.: 1 AF XY: 0.000523 AC XY: 71AN XY: 135808
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GnomAD4 exome AF: 0.000221 AC: 323AN: 1461710Hom.: 1 Cov.: 32 AF XY: 0.000272 AC XY: 198AN XY: 727166
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74354
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 22, 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