rs758951998
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4BP6_ModerateBS2
The NM_002473.6(MYH9):āc.952A>Gā(p.Met318Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Consequence
NM_002473.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.952A>G | p.Met318Val | missense_variant | 9/41 | ENST00000216181.11 | NP_002464.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.952A>G | p.Met318Val | missense_variant | 9/41 | 1 | NM_002473.6 | ENSP00000216181.6 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251490Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135918
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7AN XY: 727240
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 27, 2018 | The p.Met318Val variant in MYH9 is not expected to have clinical significance be cause it has been identified in an unaffected parent of a proband with hearing l oss by our laboratory. The thrombocytopenia and enlarged platelets (macrothromb ocytopenia) is estimated to be fully penetrant in individuals with MYH9-related disorder. Furthermore, computational prediction tools and conservation analysis suggest that this variant may not impact the protein. It has been identified i n 3/111720 European chromosomes by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org; dbSNP rs758951998). ACMG/AMP Criteria applied: BS 2; BP4; PM2. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at