rs370223713
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017534.6(MYH2):c.2304+7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,614,084 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 3 hom. )
Consequence
MYH2
NM_017534.6 splice_region, intron
NM_017534.6 splice_region, intron
Scores
2
Splicing: ADA: 0.00002242
2
Clinical Significance
Conservation
PhyloP100: -1.20
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 17-10533502-A-C is Benign according to our data. Variant chr17-10533502-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 195517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000322 (49/152204) while in subpopulation AMR AF= 0.00229 (35/15282). AF 95% confidence interval is 0.00169. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 SD gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MYH2 | NM_017534.6 | c.2304+7T>G | splice_region_variant, intron_variant | Intron 20 of 39 | ENST00000245503.10 | NP_060004.3 | ||
| MYH2 | NM_001100112.2 | c.2304+7T>G | splice_region_variant, intron_variant | Intron 20 of 39 | NP_001093582.1 | |||
| MYHAS | NR_125367.1 | n.168-34035A>C | intron_variant | Intron 2 of 10 |
Ensembl
Frequencies
GnomAD3 genomes 0.000322 AC: 49AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00115 AC: 290AN: 251398Hom.: 2 AF XY: 0.000869 AC XY: 118AN XY: 135862
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GnomAD4 exome AF: 0.000234 AC: 342AN: 1461880Hom.: 3 Cov.: 31 AF XY: 0.000208 AC XY: 151AN XY: 727248
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GnomAD4 genome 0.000322 AC: 49AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74360
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Benign:2
Jan 13, 2022
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Jan 15, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
Feb 13, 2015
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
MYH2-related disorder Benign:1
Feb 06, 2020
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at