rs137934837
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 2P and 18B. PP2PP3BP4_ModerateBP6_Very_StrongBS1BS2
The NM_002474.3(MYH11):c.4604G>A(p.Arg1535Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,614,018 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1535W) has been classified as Uncertain significance.
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.4604G>A | p.Arg1535Gln | missense_variant | 33/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.4625G>A | p.Arg1542Gln | missense_variant | 34/43 | ENST00000452625.7 | |
NDE1 | NM_017668.3 | c.948-3165C>T | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.4604G>A | p.Arg1535Gln | missense_variant | 33/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.4625G>A | p.Arg1542Gln | missense_variant | 34/43 | 1 | NM_001040113.2 | ||
NDE1 | ENST00000396354.6 | c.948-3165C>T | intron_variant | 1 | NM_017668.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00218 AC: 331AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00222 AC: 559AN: 251412Hom.: 1 AF XY: 0.00232 AC XY: 315AN XY: 135892
GnomAD4 exome AF: 0.00315 AC: 4603AN: 1461832Hom.: 7 Cov.: 32 AF XY: 0.00309 AC XY: 2245AN XY: 727228
GnomAD4 genome ? AF: 0.00217 AC: 330AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00192 AC XY: 143AN XY: 74418
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1Benign:3
Uncertain significance, no assertion criteria provided | clinical testing | Blueprint Genetics | May 19, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 29, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 05, 2018 | - - |
Aortic aneurysm, familial thoracic 4 Uncertain:1Benign:2
Uncertain significance, no assertion criteria provided | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Sep 26, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 11, 2019 | 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Mar 23, 2020 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | MYH11: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2023 | - - |
MYH11-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at