rs201676960
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002473.6(MYH9):c.5593-14G>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,607,082 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 0.0017 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
MYH9
NM_002473.6 splice_polypyrimidine_tract, intron
NM_002473.6 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.96
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 22-36284279-C-A is Benign according to our data. Variant chr22-36284279-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 164415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-36284279-C-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00167 (255/152330) while in subpopulation AFR AF= 0.0058 (241/41570). AF 95% confidence interval is 0.0052. There are 0 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 255 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.5593-14G>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.5593-14G>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002473.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00166 AC: 253AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000450 AC: 107AN: 237870Hom.: 0 AF XY: 0.000402 AC XY: 52AN XY: 129376
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GnomAD4 exome AF: 0.000164 AC: 239AN: 1454752Hom.: 0 Cov.: 35 AF XY: 0.000138 AC XY: 100AN XY: 723802
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GnomAD4 genome ? AF: 0.00167 AC: 255AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.00153 AC XY: 114AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | 5593-14G>T in Intron 39 of MYH9: This variant is not expected to have clinical s ignificance because it has been identified in 0.6% (22/3736) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | MYH9: BS1, BS2 - |
Autosomal dominant nonsyndromic hearing loss 17;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 09, 2022 | - - |
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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at