chr17-10533379-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017534.6(MYH2):c.2347C>T(p.Arg783Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R783R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017534.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.2347C>T | p.Arg783Ter | stop_gained | 21/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-34158G>A | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.2347C>T | p.Arg783Ter | stop_gained | 21/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.2347C>T | p.Arg783Ter | stop_gained | 21/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.262G>A | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251368Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135856
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727240
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2010 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 13, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 183662). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital myopathy (PMID: 20418530). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs762121316, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg783*) in the MYH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYH2 are known to be pathogenic (PMID: 20418530, 23388406, 24193343). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at