17-10521369-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017534.6(MYH2):c.5737G>A(p.Glu1913Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017534.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.5737G>A | p.Glu1913Lys | missense_variant | Exon 40 of 40 | ENST00000245503.10 | NP_060004.3 | |
MYH2 | NM_001100112.2 | c.5737G>A | p.Glu1913Lys | missense_variant | Exon 40 of 40 | NP_001093582.1 | ||
MYHAS | NR_125367.1 | n.168-46168C>T | intron_variant | Intron 2 of 10 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135884
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727232
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.5737G>A (p.E1913K) alteration is located in exon 40 (coding exon 38) of the MYH2 gene. This alteration results from a G to A substitution at nucleotide position 5737, causing the glutamic acid (E) at amino acid position 1913 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Myopathy, proximal, and ophthalmoplegia Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant has not been reported in the literature in individuals affected with MYH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 1913 of the MYH2 protein (p.Glu1913Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. -
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at