16-15732552-AAAAAGCA-AA
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_002474.3(MYH11):c.3651+6_3651+11del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
MYH11
NM_002474.3 splice_donor_region, intron
NM_002474.3 splice_donor_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.85
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 16-15732552-AAAAAGC-A is Benign according to our data. Variant chr16-15732552-AAAAAGC-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 201030.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2, Benign=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_001040113.2 | c.3672+6_3672+11del | splice_donor_region_variant, intron_variant | ENST00000452625.7 | |||
MYH11 | NM_002474.3 | c.3651+6_3651+11del | splice_donor_region_variant, intron_variant | ENST00000300036.6 | |||
MYH11 | NM_001040114.2 | c.3672+6_3672+11del | splice_donor_region_variant, intron_variant | ||||
MYH11 | NM_022844.3 | c.3651+6_3651+11del | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.3651+6_3651+11del | splice_donor_region_variant, intron_variant | 1 | NM_002474.3 | P3 | |||
MYH11 | ENST00000452625.7 | c.3672+6_3672+11del | splice_donor_region_variant, intron_variant | 1 | NM_001040113.2 | ||||
ENST00000574212.1 | n.397_402del | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 15, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2013 | The variant is found in TAAD panel(s). - |
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Apr 02, 2019 | - - |
Aortic aneurysm, familial thoracic 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | MYH11: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at