22-36296899-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002473.6(MYH9):c.3216G>A(p.Ala1072=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000469 in 1,613,552 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 4 hom. )
Consequence
MYH9
NM_002473.6 synonymous
NM_002473.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.37
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=-0.53).
BP6
Variant 22-36296899-C-T is Benign according to our data. Variant chr22-36296899-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.37 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000559 (85/152186) while in subpopulation NFE AF= 0.00106 (72/68036). AF 95% confidence interval is 0.000861. There are 0 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 85 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.3216G>A | p.Ala1072= | synonymous_variant | 25/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.3216G>A | p.Ala1072= | synonymous_variant | 25/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.3279G>A | p.Ala1093= | synonymous_variant | 26/42 | ||||
MYH9 | ENST00000459960.1 | n.425G>A | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
MYH9 | ENST00000691109.1 | n.3511G>A | non_coding_transcript_exon_variant | 19/35 |
Frequencies
GnomAD3 genomes AF: 0.000559 AC: 85AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000415 AC: 104AN: 250894Hom.: 1 AF XY: 0.000479 AC XY: 65AN XY: 135744
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GnomAD4 exome AF: 0.000459 AC: 671AN: 1461366Hom.: 4 Cov.: 31 AF XY: 0.000486 AC XY: 353AN XY: 726936
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GnomAD4 genome AF: 0.000559 AC: 85AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000498 AC XY: 37AN XY: 74352
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | MYH9: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2019 | - - |
MYH9-related disorder Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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. - |
Autosomal dominant nonsyndromic hearing loss 17 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2017 | p.Ala1072Ala in Exon 25 of MYH9: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.1% (112/ 126526) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnoma d.broadinstitute.org; dbSNP rs139441456). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at