NM_002473.6:c.705+15G>A
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002473.6(MYH9):c.705+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,613,438 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: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
MYH9
NM_002473.6 intron
NM_002473.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.49
Publications
0 publications found
Genes affected
MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]
MYH9 Gene-Disease associations (from GenCC):
- autosomal dominant nonsyndromic hearing loss 17Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing lossInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
- May-Hegglin anomalyInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 22-36322414-C-T is Benign according to our data. Variant chr22-36322414-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 258764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000158 (24/152264) while in subpopulation AMR AF = 0.000262 (4/15290). AF 95% confidence interval is 0.000102. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High AC in GnomAd4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.705+15G>A | intron_variant | Intron 6 of 40 | ENST00000216181.11 | NP_002464.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152264Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
24
AN:
152264
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000797 AC: 20AN: 250852 AF XY: 0.0000589 show subpopulations
GnomAD2 exomes
AF:
AC:
20
AN:
250852
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000114 AC: 166AN: 1461174Hom.: 0 Cov.: 31 AF XY: 0.0000990 AC XY: 72AN XY: 726956 show subpopulations
GnomAD4 exome
AF:
AC:
166
AN:
1461174
Hom.:
Cov.:
31
AF XY:
AC XY:
72
AN XY:
726956
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33468
American (AMR)
AF:
AC:
4
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26122
East Asian (EAS)
AF:
AC:
1
AN:
39694
South Asian (SAS)
AF:
AC:
0
AN:
86246
European-Finnish (FIN)
AF:
AC:
0
AN:
53104
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
150
AN:
1111674
Other (OTH)
AF:
AC:
10
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
10
20
30
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<30
30-35
35-40
40-45
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55-60
60-65
65-70
70-75
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>80
Age
GnomAD4 genome AF: 0.000158 AC: 24AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74392 show subpopulations
GnomAD4 genome
AF:
AC:
24
AN:
152264
Hom.:
Cov.:
33
AF XY:
AC XY:
8
AN XY:
74392
show subpopulations
African (AFR)
AF:
AC:
8
AN:
41480
American (AMR)
AF:
AC:
4
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5194
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
12
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.527
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Autosomal dominant nonsyndromic hearing loss 17;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Benign:1
Apr 27, 2022
Fulgent Genetics, Fulgent Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
Jan 14, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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