16-15745203-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_002474.3(MYH11):c.2446A>C(p.Met816Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.2446A>C | p.Met816Leu | missense_variant | 20/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.2467A>C | p.Met823Leu | missense_variant | 21/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.2467A>C | p.Met823Leu | missense_variant | 21/42 | ||
MYH11 | NM_022844.3 | c.2446A>C | p.Met816Leu | missense_variant | 20/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.2446A>C | p.Met816Leu | missense_variant | 20/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.2467A>C | p.Met823Leu | missense_variant | 21/43 | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151846Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251400Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135868
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461594Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727092
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151846Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74178
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 30, 2018 | Variant summary: MYH11 c.2467A>C (p.Met823Leu) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246192 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2467A>C in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Aortic aneurysm, familial thoracic 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 823 of the MYH11 protein (p.Met823Leu). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 632912). 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 C0"). 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