rs200893594
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_017534.6(MYH2):c.979G>A(p.Asp327Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH2 | NM_017534.6 | c.979G>A | p.Asp327Asn | missense_variant | 11/40 | ENST00000245503.10 | |
MYHAS | NR_125367.1 | n.168-26914C>T | intron_variant, non_coding_transcript_variant | ||||
MYH2 | NM_001100112.2 | c.979G>A | p.Asp327Asn | missense_variant | 11/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH2 | ENST00000245503.10 | c.979G>A | p.Asp327Asn | missense_variant | 11/40 | 1 | NM_017534.6 | P1 | |
MYH2 | ENST00000532183.6 | c.979G>A | p.Asp327Asn | missense_variant | 10/17 | 1 | |||
MYH2 | ENST00000622564.4 | c.979G>A | p.Asp327Asn | missense_variant | 11/18 | 1 | |||
MYH2 | ENST00000397183.6 | c.979G>A | p.Asp327Asn | missense_variant | 11/40 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249556Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135074
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461166Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21AN XY: 726952
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74434
ClinVar
Submissions by phenotype
Myopathy, proximal, and ophthalmoplegia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 07, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 327 of the MYH2 protein (p.Asp327Asn). This variant is present in population databases (rs200893594, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with MYH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 577587). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH2 protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at