rs147122501
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_002473.6(MYH9):c.136C>T(p.Leu46Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,614,202 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002473.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.136C>T | p.Leu46Phe | missense_variant | Exon 2 of 41 | ENST00000216181.11 | NP_002464.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00521 AC: 793AN: 152196Hom.: 12 Cov.: 32
GnomAD3 exomes AF: 0.00604 AC: 1519AN: 251398Hom.: 27 AF XY: 0.00601 AC XY: 817AN XY: 135886
GnomAD4 exome AF: 0.00445 AC: 6503AN: 1461888Hom.: 62 Cov.: 34 AF XY: 0.00435 AC XY: 3167AN XY: 727242
GnomAD4 genome AF: 0.00521 AC: 793AN: 152314Hom.: 12 Cov.: 32 AF XY: 0.00699 AC XY: 521AN XY: 74482
ClinVar
Submissions by phenotype
not provided Benign:7
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This variant is associated with the following publications: (PMID: 30245029, 29090586, 29110756, 25077172, 24130771) -
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MYH9: BS1 -
not specified Benign:4
Leu46Phe in exon 2 of MYH9: This variant is not expected to have clinical signif icance because it has been identified in 4.5% (295/6600) of Finnish chromosomes including 5 homozygotes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs147122501). -
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Autosomal dominant nonsyndromic hearing loss 17 Benign:1
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. -
MYH9-related disorder Benign:1
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;C4551953:Vitelliform macular dystrophy 1;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Other:1
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at