chr17-10533312-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_017534.6(MYH2):āc.2414T>Cā(p.Val805Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,613,884 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017534.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.2414T>C | p.Val805Ala | missense_variant | Exon 21 of 40 | ENST00000245503.10 | NP_060004.3 | |
MYH2 | NM_001100112.2 | c.2414T>C | p.Val805Ala | missense_variant | Exon 21 of 40 | NP_001093582.1 | ||
MYHAS | NR_125367.1 | n.168-34225A>G | intron_variant | Intron 2 of 10 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000487 AC: 74AN: 151934Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000748 AC: 188AN: 251434Hom.: 2 AF XY: 0.000648 AC XY: 88AN XY: 135880
GnomAD4 exome AF: 0.000388 AC: 567AN: 1461832Hom.: 5 Cov.: 31 AF XY: 0.000355 AC XY: 258AN XY: 727220
GnomAD4 genome AF: 0.000487 AC: 74AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.000498 AC XY: 37AN XY: 74332
ClinVar
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Pathogenic:1Uncertain:1Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -
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not provided Uncertain:1Benign:1
BS1 -
This variant is associated with the following publications: (PMID: 22349865, 27066573) -
not specified Uncertain:1
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1.1% East Asian ExAC, 2 homozygotes, not in ClinVar. Cai 2011 reported the variant in 3/21 Jpanese patients with inclusion body myositis. Clinical features of IBM include adult-onset weakness of proximal or distal muscle and normal or slightly elevated serum creatine kinase (CK) level. This variant has not been associated with myopathy ith external ophthalmoplegia. Therefore, despite of the classification of the variant, I do not think the disease meets criteria for reporting in BabySeq. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at