rs147329431
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_033118.4(MYLK2):c.1356G>A(p.Glu452=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,614,050 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
MYLK2
NM_033118.4 synonymous
NM_033118.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.128
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant 20-31831073-G-A is Benign according to our data. Variant chr20-31831073-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 518318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-31831073-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.128 with no splicing effect.
BS2
?
High AC in GnomAd4 at 9 AD,Digenic gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK2 | NM_033118.4 | c.1356G>A | p.Glu452= | synonymous_variant | 10/13 | ENST00000375985.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK2 | ENST00000375985.5 | c.1356G>A | p.Glu452= | synonymous_variant | 10/13 | 1 | NM_033118.4 | P1 | |
MYLK2 | ENST00000375994.6 | c.1356G>A | p.Glu452= | synonymous_variant | 9/12 | 1 | P1 | ||
MYLK2 | ENST00000468730.1 | n.294G>A | non_coding_transcript_exon_variant | 3/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251478Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135908
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GnomAD4 exome AF: 0.000131 AC: 191AN: 1461878Hom.: 0 Cov.: 37 AF XY: 0.000143 AC XY: 104AN XY: 727242
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74328
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypertrophic cardiomyopathy 1 Benign:3
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Feb 21, 2017 | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at