14-23389062-AGGG-AG
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_002471.4(MYH6):c.3979-9_3979-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 763 hom., cov: 0)
Exomes 𝑓: 0.14 ( 11301 hom. )
Failed GnomAD Quality Control
Consequence
MYH6
NM_002471.4 splice_region, splice_polypyrimidine_tract, intron
NM_002471.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.275
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 -16 ACMG points.
BP6
?
Variant 14-23389062-AGG-A is Benign according to our data. Variant chr14-23389062-AGG-A is described in ClinVar as [Benign]. Clinvar id is 220788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23389062-AGG-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.3979-9_3979-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.3979-9_3979-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.129 AC: 14951AN: 115620Hom.: 761 Cov.: 0
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GnomAD3 exomes AF: 0.122 AC: 17018AN: 139674Hom.: 903 AF XY: 0.120 AC XY: 9184AN XY: 76278
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.141 AC: 149380AN: 1057912Hom.: 11301 AF XY: 0.137 AC XY: 72412AN XY: 527248
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GnomAD4 genome ? AF: 0.129 AC: 14958AN: 115736Hom.: 763 Cov.: 0 AF XY: 0.125 AC XY: 7118AN XY: 56878
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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, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 16, 2019 | - - |
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 | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 07, 2017 | 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. - |
Hypertrophic cardiomyopathy 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 08, 2018 | - - |
Computational scores
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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