rs117562194
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017534.6(MYH2):c.2062+8A>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 0.000621 in 1,614,016 control chromosomes in the GnomAD database, including 14 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
Consequence
NM_017534.6 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.2062+8A>G | splice_region_variant, intron_variant | ENST00000245503.10 | |||
MYHAS | NR_125367.1 | n.168-32267T>C | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.2062+8A>G | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.2062+8A>G | splice_region_variant, intron_variant | 1 | NM_017534.6 | P1 | |||
ENST00000399342.6 | n.370+1783T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000559 AC: 85AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00127 AC: 319AN: 251284Hom.: 8 AF XY: 0.00113 AC XY: 154AN XY: 135836
GnomAD4 exome AF: 0.000627 AC: 916AN: 1461790Hom.: 14 Cov.: 32 AF XY: 0.000584 AC XY: 425AN XY: 727214
GnomAD4 genome ? AF: 0.000565 AC: 86AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45AN XY: 74418
ClinVar
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 21, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at