rs76757102
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_016599.5(MYOZ2):āc.29A>Cā(p.Gln10Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00107 in 1,613,748 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q10R) has been classified as Uncertain significance.
Frequency
Consequence
NM_016599.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOZ2 | NM_016599.5 | c.29A>C | p.Gln10Pro | missense_variant | 2/6 | ENST00000307128.6 | |
MYOZ2 | XM_006714234.5 | c.29A>C | p.Gln10Pro | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOZ2 | ENST00000307128.6 | c.29A>C | p.Gln10Pro | missense_variant | 2/6 | 1 | NM_016599.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00125 AC: 190AN: 152248Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00264 AC: 662AN: 250898Hom.: 12 AF XY: 0.00265 AC XY: 359AN XY: 135592
GnomAD4 exome AF: 0.00105 AC: 1540AN: 1461382Hom.: 28 Cov.: 31 AF XY: 0.00109 AC XY: 793AN XY: 726990
GnomAD4 genome ? AF: 0.00125 AC: 190AN: 152366Hom.: 6 Cov.: 32 AF XY: 0.00153 AC XY: 114AN XY: 74506
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 18, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 20, 2012 | Gln10Pro in exon 2 of MYOZ2: This variant is not expected to have clinical signi ficance because it has been identified in 4.2% (24/572) of Asian chromosomes fro m a broad population by the 1000 Genomes project (dbSNP rs76757102). - |
Hypertrophic cardiomyopathy 16 Benign:3
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | May 31, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Jul 28, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 13, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 25, 2017 | Variant summary: The MYOZ2 c.29A>C (p.Gln10Pro) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 320/118584 control chromosomes (5 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.033583 (287/8546). This frequency is about 1343 times the estimated maximal expected allele frequency of a pathogenic MYOZ2 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories in ClinVar have classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature, nor has it been functionally characterized. Taken together, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Feb 07, 2018 | - - |
Hypertrophic cardiomyopathy;C0878544:Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Jan 31, 2019 | - - |
Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 04, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at