rs779257410
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_017534.6(MYH2):c.4000G>T(p.Ala1334Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1334T) has been classified 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.4000G>T | p.Ala1334Ser | missense_variant | 30/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-40751C>A | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.4000G>T | p.Ala1334Ser | missense_variant | 30/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.4000G>T | p.Ala1334Ser | missense_variant | 30/40 | 1 | NM_017534.6 | P1 | |
ENST00000399342.6 | n.207-6538C>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251330Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135854
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727246
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 12, 2017 | This sequence change replaces alanine with serine at codon 1334 of the MYH2 protein (p.Ala1334Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs779257410, ExAC 0.001%). This variant has not been reported in the literature in individuals with a MYH2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on MYH2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 03, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at