rs142654744
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS1
The NM_002474.3(MYH11):c.5450C>T(p.Ala1817Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1817T) has been classified as Uncertain significance.
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.5450C>T | p.Ala1817Val | missense_variant | 38/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.5471C>T | p.Ala1824Val | missense_variant | 39/43 | ENST00000452625.7 | |
NDE1 | NM_017668.3 | c.948-6997G>A | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.5450C>T | p.Ala1817Val | missense_variant | 38/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.5471C>T | p.Ala1824Val | missense_variant | 39/43 | 1 | NM_001040113.2 | ||
NDE1 | ENST00000396354.6 | c.948-6997G>A | intron_variant | 1 | NM_017668.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251326Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135842
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461872Hom.: 0 Cov.: 73 AF XY: 0.0000289 AC XY: 21AN XY: 727236
GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22AN XY: 74340
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 03, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 22, 2021 | The p.A1817V variant (also known as c.5450C>T), located in coding exon 37 of the MYH11 gene, results from a C to T substitution at nucleotide position 5450. The alanine at codon 1817 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 30, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2023 | Has not been previously published as pathogenic or benign in association with TAAD to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 18391202, 21529752) - |
Aortic aneurysm, familial thoracic 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | - - |
MYH11-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 02, 2020 | 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 | Jun 01, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at