rs452036
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002471.4(MYH6):c.2292+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,750 control chromosomes in the GnomAD database, including 107,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.42 ( 14545 hom., cov: 33)
Exomes 𝑓: 0.35 ( 93315 hom. )
Consequence
MYH6
NM_002471.4 intron
NM_002471.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.65
Genes affected
MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]
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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=-0.96).
BP6
?
Variant 14-23396676-G-A is Benign according to our data. Variant chr14-23396676-G-A is described in ClinVar as [Benign]. Clinvar id is 258709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23396676-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.2292+18C>T | intron_variant | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.2292+18C>T | intron_variant | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.415 AC: 63087AN: 152036Hom.: 14498 Cov.: 33
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GnomAD3 exomes AF: 0.328 AC: 82470AN: 251054Hom.: 15041 AF XY: 0.328 AC XY: 44492AN XY: 135680
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GnomAD4 exome AF: 0.350 AC: 511550AN: 1461596Hom.: 93315 Cov.: 53 AF XY: 0.348 AC XY: 253247AN XY: 727110
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GnomAD4 genome ? AF: 0.415 AC: 63187AN: 152154Hom.: 14545 Cov.: 33 AF XY: 0.408 AC XY: 30361AN XY: 74406
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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:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Hypertrophic cardiomyopathy 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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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