rs368822172
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP6
The NM_053025.4(MYLK):c.256C>T(p.Arg86Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R86Q) has been classified as Likely benign.
Frequency
Consequence
NM_053025.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.256C>T | p.Arg86Trp | missense_variant | 5/34 | ENST00000360304.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.256C>T | p.Arg86Trp | missense_variant | 5/34 | 5 | NM_053025.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000250 AC: 38AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 36AN: 251188Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135764
GnomAD4 exome AF: 0.000101 AC: 148AN: 1461874Hom.: 0 Cov.: 32 AF XY: 0.0000921 AC XY: 67AN XY: 727240
GnomAD4 genome ? AF: 0.000250 AC: 38AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74462
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 7 Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, no assertion criteria provided | clinical testing | Knight Diagnostic Laboratories, Oregon Health and Sciences University | Sep 26, 2015 | - - |
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 31, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 24, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 02, 2022 | BS1 - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 18, 2023 | The p.R86W variant (also known as c.256C>T), located in coding exon 2 of the MYLK gene, results from a C to T substitution at nucleotide position 256. The arginine at codon 86 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in a brain arteriovenous malformation cohort and an ischemic stroke cohort (Zhang M et al. J Neurointerv Surg, 2021 Jun;13:568-573; Alkhamis FA et al. Funct Integr Genomics, 2023 Mar;23:102). This amino acid position is highly 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. - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 26, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at