rs750642581
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_002474.3(MYH11):āc.1823A>Gā(p.Asn608Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,986 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N608D) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.1823A>G | p.Asn608Ser | missense_variant | 15/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.1844A>G | p.Asn615Ser | missense_variant | 16/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.1844A>G | p.Asn615Ser | missense_variant | 16/42 | ||
MYH11 | NM_022844.3 | c.1823A>G | p.Asn608Ser | missense_variant | 15/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.1823A>G | p.Asn608Ser | missense_variant | 15/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.1844A>G | p.Asn615Ser | missense_variant | 16/43 | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251488Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135922
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461860Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727234
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 2022 | The p.N608S variant (also known as c.1823A>G), located in coding exon 14 of the MYH11 gene, results from an A to G substitution at nucleotide position 1823. The asparagine at codon 608 is replaced by serine, an amino acid with highly similar properties. This amino acid position is 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. - |
Aortic aneurysm, familial thoracic 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 615 of the MYH11 protein (p.Asn615Ser). This variant is present in population databases (rs750642581, gnomAD 0.04%). 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: 405478). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at