16-15703925-GTTTTT-GTTTTTTT
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_002474.3(MYH11):c.*64_*65dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,606,348 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MYH11
NM_002474.3 3_prime_UTR
NM_002474.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.794
Publications
1 publications found
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]
NDE1 Gene-Disease associations (from GenCC):
- lissencephaly 4Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- hydranencephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- microlissencephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- NDE1-related microhydranencephalyInheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.*64_*65dupAA | 3_prime_UTR_variant | Exon 41 of 41 | ENST00000300036.6 | NP_002465.1 | ||
MYH11 | NM_001040113.2 | c.*205_*206dupAA | 3_prime_UTR_variant | Exon 43 of 43 | ENST00000452625.7 | NP_001035202.1 | ||
NDE1 | NM_017668.3 | c.947+7072_947+7073dupTT | intron_variant | Intron 8 of 8 | ENST00000396354.6 | NP_060138.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.*64_*65dupAA | 3_prime_UTR_variant | Exon 41 of 41 | 1 | NM_002474.3 | ENSP00000300036.5 | |||
MYH11 | ENST00000452625.7 | c.*205_*206dupAA | 3_prime_UTR_variant | Exon 43 of 43 | 1 | NM_001040113.2 | ENSP00000407821.2 | |||
NDE1 | ENST00000396354.6 | c.947+7072_947+7073dupTT | intron_variant | Intron 8 of 8 | 1 | NM_017668.3 | ENSP00000379642.1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151688Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151688
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1454660Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724022 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3
AN:
1454660
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
724022
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
3
AN:
33326
American (AMR)
AF:
AC:
0
AN:
44674
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26078
East Asian (EAS)
AF:
AC:
0
AN:
39578
South Asian (SAS)
AF:
AC:
0
AN:
85804
European-Finnish (FIN)
AF:
AC:
0
AN:
53040
Middle Eastern (MID)
AF:
AC:
0
AN:
5676
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1106390
Other (OTH)
AF:
AC:
0
AN:
60094
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.024570), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.358
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151688Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74082 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151688
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74082
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41212
American (AMR)
AF:
AC:
0
AN:
15212
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5178
South Asian (SAS)
AF:
AC:
0
AN:
4790
European-Finnish (FIN)
AF:
AC:
0
AN:
10546
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67964
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.