NM_002474.3:c.*61_*65delAAAAA
Variant summary
Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_002474.3(MYH11):c.*61_*65delAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,606,394 control chromosomes in the GnomAD database, including 171 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0090 ( 10 hom., cov: 32)
Exomes 𝑓: 0.012 ( 161 hom. )
Consequence
MYH11
NM_002474.3 3_prime_UTR
NM_002474.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.27
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
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -16 ACMG points.
BP6
Variant 16-15703925-GTTTTT-G is Benign according to our data. Variant chr16-15703925-GTTTTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 318085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00895 (1359/151808) while in subpopulation NFE AF = 0.0128 (867/67956). AF 95% confidence interval is 0.0121. There are 10 homozygotes in GnomAd4. There are 720 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 10 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.*61_*65delAAAAA | 3_prime_UTR_variant | Exon 41 of 41 | ENST00000300036.6 | NP_002465.1 | ||
MYH11 | NM_001040113.2 | c.*202_*206delAAAAA | 3_prime_UTR_variant | Exon 43 of 43 | ENST00000452625.7 | NP_001035202.1 | ||
NDE1 | NM_017668.3 | c.947+7069_947+7073delTTTTT | 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.*61_*65delAAAAA | 3_prime_UTR_variant | Exon 41 of 41 | 1 | NM_002474.3 | ENSP00000300036.5 | |||
MYH11 | ENST00000452625.7 | c.*202_*206delAAAAA | 3_prime_UTR_variant | Exon 43 of 43 | 1 | NM_001040113.2 | ENSP00000407821.2 | |||
NDE1 | ENST00000396354.6 | c.947+7069_947+7073delTTTTT | intron_variant | Intron 8 of 8 | 1 | NM_017668.3 | ENSP00000379642.1 |
Frequencies
GnomAD3 genomes AF: 0.00897 AC: 1361AN: 151690Hom.: 10 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1361
AN:
151690
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:
GnomAD2 exomes AF: 0.00969 AC: 2420AN: 249778 AF XY: 0.00979 show subpopulations
GnomAD2 exomes
AF:
AC:
2420
AN:
249778
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0121 AC: 17610AN: 1454586Hom.: 161 AF XY: 0.0118 AC XY: 8553AN XY: 723982 show subpopulations
GnomAD4 exome
AF:
AC:
17610
AN:
1454586
Hom.:
AF XY:
AC XY:
8553
AN XY:
723982
show subpopulations
African (AFR)
AF:
AC:
63
AN:
33326
American (AMR)
AF:
AC:
138
AN:
44674
Ashkenazi Jewish (ASJ)
AF:
AC:
50
AN:
26078
East Asian (EAS)
AF:
AC:
0
AN:
39578
South Asian (SAS)
AF:
AC:
281
AN:
85804
European-Finnish (FIN)
AF:
AC:
1629
AN:
53038
Middle Eastern (MID)
AF:
AC:
26
AN:
5674
European-Non Finnish (NFE)
AF:
AC:
14811
AN:
1106320
Other (OTH)
AF:
AC:
612
AN:
60094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
764
1528
2292
3056
3820
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00895 AC: 1359AN: 151808Hom.: 10 Cov.: 32 AF XY: 0.00970 AC XY: 720AN XY: 74212 show subpopulations
GnomAD4 genome
AF:
AC:
1359
AN:
151808
Hom.:
Cov.:
32
AF XY:
AC XY:
720
AN XY:
74212
show subpopulations
African (AFR)
AF:
AC:
81
AN:
41336
American (AMR)
AF:
AC:
43
AN:
15232
Ashkenazi Jewish (ASJ)
AF:
AC:
6
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5166
South Asian (SAS)
AF:
AC:
14
AN:
4786
European-Finnish (FIN)
AF:
AC:
337
AN:
10546
Middle Eastern (MID)
AF:
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
AC:
867
AN:
67956
Other (OTH)
AF:
AC:
10
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
68
136
205
273
341
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Jun 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
MYH11: BS1, BS2; NDE1: BS1, BS2 -
Aug 19, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Lissencephaly, Recessive Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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