rs875725
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002473.6(MYH9):āc.3345A>Gā(p.Glu1115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,613,868 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.031 ( 120 hom., cov: 32)
Exomes š: 0.014 ( 284 hom. )
Consequence
MYH9
NM_002473.6 synonymous
NM_002473.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.392
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 22-36295645-T-C is Benign according to our data. Variant chr22-36295645-T-C is described in ClinVar as [Benign]. Clinvar id is 44558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36295645-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.392 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.3345A>G | p.Glu1115= | synonymous_variant | 26/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.3345A>G | p.Glu1115= | synonymous_variant | 26/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.3408A>G | p.Glu1136= | synonymous_variant | 27/42 | ||||
MYH9 | ENST00000459960.1 | n.554A>G | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
MYH9 | ENST00000691109.1 | n.3640A>G | non_coding_transcript_exon_variant | 20/35 |
Frequencies
GnomAD3 genomes ? AF: 0.0310 AC: 4717AN: 152112Hom.: 120 Cov.: 32
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GnomAD3 exomes AF: 0.0168 AC: 4205AN: 250798Hom.: 67 AF XY: 0.0153 AC XY: 2081AN XY: 135670
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GnomAD4 exome AF: 0.0144 AC: 21011AN: 1461638Hom.: 284 Cov.: 35 AF XY: 0.0140 AC XY: 10190AN XY: 727106
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GnomAD4 genome ? AF: 0.0310 AC: 4722AN: 152230Hom.: 120 Cov.: 32 AF XY: 0.0305 AC XY: 2270AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Glu1115Glu in Exon 26 of MYH9: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 7.7% (287/3734) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs875725). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 15, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Autosomal dominant nonsyndromic hearing loss 17 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Atypical hemolytic-uremic syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 06, 2022 | - - |
MYH9-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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