rs148682361
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_002474.3(MYH11):c.2412-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,340 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: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
MYH11
NM_002474.3 splice_polypyrimidine_tract, intron
NM_002474.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002929
2
Clinical Significance
Conservation
PhyloP100: -0.414
Genes affected
MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 16-15745246-G-A is Benign according to our data. Variant chr16-15745246-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1331760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_001040113.2 | c.2433-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000452625.7 | |||
MYH11 | NM_002474.3 | c.2412-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000300036.6 | |||
MYH11 | NM_001040114.2 | c.2433-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
MYH11 | NM_022844.3 | c.2412-9C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.2412-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002474.3 | P3 | |||
MYH11 | ENST00000452625.7 | c.2433-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250446Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135412
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458340Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 725652
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 22, 2021 | - - |
Aortic aneurysm, familial thoracic 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 08, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at