rs76530988
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000375985.5(MYLK2):c.1082+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,614,012 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.019 ( 42 hom., cov: 31)
Exomes 𝑓: 0.025 ( 566 hom. )
Consequence
MYLK2
ENST00000375985.5 intron
ENST00000375985.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.02
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 20-31826725-G-A is Benign according to our data. Variant chr20-31826725-G-A is described in ClinVar as [Benign]. Clinvar id is 36649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31826725-G-A is described in Lovd as [Benign]. Variant chr20-31826725-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2923/152168) while in subpopulation NFE AF= 0.0278 (1890/67988). AF 95% confidence interval is 0.0268. There are 42 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2923 AD,Digenic gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYLK2 | NM_033118.4 | c.1082+11G>A | intron_variant | ENST00000375985.5 | NP_149109.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYLK2 | ENST00000375985.5 | c.1082+11G>A | intron_variant | 1 | NM_033118.4 | ENSP00000365152 | P1 | |||
MYLK2 | ENST00000375994.6 | c.1082+11G>A | intron_variant | 1 | ENSP00000365162 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0192 AC: 2926AN: 152050Hom.: 42 Cov.: 31
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GnomAD3 exomes AF: 0.0203 AC: 5105AN: 251324Hom.: 92 AF XY: 0.0205 AC XY: 2782AN XY: 135856
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GnomAD4 exome AF: 0.0250 AC: 36576AN: 1461844Hom.: 566 Cov.: 33 AF XY: 0.0244 AC XY: 17719AN XY: 727216
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GnomAD4 genome AF: 0.0192 AC: 2923AN: 152168Hom.: 42 Cov.: 31 AF XY: 0.0192 AC XY: 1432AN XY: 74404
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 27, 2011 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | curation | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 18, 2011 | - - |
Hypertrophic cardiomyopathy 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at