rs397516781
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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.705+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,613,582 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000066 ( 2 hom. )
Consequence
MYH9
NM_002473.6 intron
NM_002473.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.32
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=-0.85).
BP6
?
Variant 22-36322420-G-A is Benign according to our data. Variant chr22-36322420-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 44574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000664 (97/1461330) while in subpopulation AMR AF= 0.000134 (6/44718). AF 95% confidence interval is 0.0000712. There are 2 homozygotes in gnomad4_exome. There are 51 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 97 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.705+9C>T | intron_variant | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.705+9C>T | intron_variant | 1 | NM_002473.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000104 AC: 26AN: 251074Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135822
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GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461330Hom.: 2 Cov.: 31 AF XY: 0.0000701 AC XY: 51AN XY: 727020
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74386
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 20, 2012 | 705+9C>T in Intron 6 of MYH9: This variant is not expected to have clinical sign ificance because it is not located within the conserved region of the splice con sensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
MYH9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 23, 2021 | 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). - |
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