chr14-23382056-A-AT
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_ModerateBS2
The NM_002471.4(MYH6):c.5803dupA(p.Met1935AsnfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002471.4 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.5803dupA | p.Met1935AsnfsTer4 | frameshift_variant | Exon 39 of 39 | ENST00000405093.9 | NP_002462.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727236
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:1
Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation as the last 5 amino acids are replaced with 3 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge -
Dilated cardiomyopathy 1EE;C2750467:Hypertrophic cardiomyopathy 14 Uncertain:1
The c.5803dup p.(Met1935AsnfsTer4) variant identified in the MYH6 gene has been deposited in the ClinVar database as a variant of uncertain significance [ClinVar ID:1695783]. The c.5803dup variant is observed in 7 alleles (~0.0011% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.5803dup variant is located in the last exon of this 17-exon gene and alters the wild-type translational reading frame. The resultant mutant mRNA is predicted to escape nonsense-mediated mRNA decay. If translated, the mutant protein would lack the last 5 amino acids compared to the full length 1939 amino acid protein and instead would include 3 different amino acids p.(Met1935AsnfsTer4). Based on available evidence, this c.5803dup p.(Met1935AsnfsTer4) variant in MYH6 is reported as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at