chr14-23404731-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_002471.4(MYH6):c.622G>A(p.Asp208Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00674 in 1,614,128 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002471.4 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 rank | MANE | Protein | UniProt |
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MYH6 | NM_002471.4 | c.622G>A | p.Asp208Asn | missense_variant | Exon 7 of 39 | ENST00000405093.9 | NP_002462.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00415 AC: 632AN: 152174Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00486 AC: 1223AN: 251482Hom.: 7 AF XY: 0.00514 AC XY: 699AN XY: 135916
GnomAD4 exome AF: 0.00701 AC: 10242AN: 1461836Hom.: 48 Cov.: 33 AF XY: 0.00697 AC XY: 5071AN XY: 727224
GnomAD4 genome AF: 0.00414 AC: 631AN: 152292Hom.: 2 Cov.: 32 AF XY: 0.00384 AC XY: 286AN XY: 74450
ClinVar
Submissions by phenotype
not provided Benign:7
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MYH6: BS1, BS2 -
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not specified Benign:6
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p.Asp208Asn in exon 7 of MYH6: This variant is not expected to have clinical sig nificance because it has been identified in 0.8% (554/67686) of European chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs142027794). -
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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. -
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Hypertrophic cardiomyopathy 14 Benign:1
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Cardiomyopathy Benign:1
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Heart failure Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: 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