rs199791180
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_033118.4(MYLK2):c.226C>T(p.Pro76Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P76L) has been classified as Uncertain significance.
Frequency
Consequence
NM_033118.4 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 |
---|---|---|---|---|---|---|---|
MYLK2 | NM_033118.4 | c.226C>T | p.Pro76Ser | missense_variant | 3/13 | ENST00000375985.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK2 | ENST00000375985.5 | c.226C>T | p.Pro76Ser | missense_variant | 3/13 | 1 | NM_033118.4 | P1 | |
MYLK2 | ENST00000375994.6 | c.226C>T | p.Pro76Ser | missense_variant | 2/12 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249386Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135370
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461178Hom.: 0 Cov.: 32 AF XY: 0.0000426 AC XY: 31AN XY: 726878
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Hypertrophic cardiomyopathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2022 | 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 MYLK2 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 191737). This variant has not been reported in the literature in individuals affected with MYLK2-related conditions. This variant is present in population databases (rs199791180, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 76 of the MYLK2 protein (p.Pro76Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at