rs747642850
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1
The NM_001040113.2(MYH11):c.5808-11_5808-8del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000424 in 1,609,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 0 hom. )
Consequence
MYH11
NM_001040113.2 splice_region, splice_polypyrimidine_tract, intron
NM_001040113.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.42
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]
NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP6
?
Variant 16-15708848-CAGAG-C is Benign according to our data. Variant chr16-15708848-CAGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 201040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-15708848-CAGAG-C is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000414 (63/152264) while in subpopulation AMR AF= 0.00118 (18/15286). AF 95% confidence interval is 0.000761. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_001040113.2 | c.5808-11_5808-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000452625.7 | |||
MYH11 | NM_002474.3 | c.5787-4729_5787-4726del | intron_variant | ENST00000300036.6 | |||
NDE1 | NM_017668.3 | c.947+11994_947+11997del | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.5787-4729_5787-4726del | intron_variant | 1 | NM_002474.3 | P3 | |||
NDE1 | ENST00000396354.6 | c.947+11994_947+11997del | intron_variant | 1 | NM_017668.3 | P1 | |||
MYH11 | ENST00000452625.7 | c.5808-11_5808-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001040113.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000420 AC: 102AN: 242886Hom.: 0 AF XY: 0.000427 AC XY: 56AN XY: 131050
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GnomAD4 exome AF: 0.000425 AC: 620AN: 1457426Hom.: 0 AF XY: 0.000418 AC XY: 303AN XY: 724386
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 29, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 29, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2013 | The variant is found in TAAD panel(s). - |
Aortic aneurysm, familial thoracic 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 20, 2023 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 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