rs758365123
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000355349.4(MYH7):c.2286+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000355349.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.2286+7A>G | splice_region_variant, intron_variant | ENST00000355349.4 | NP_000248.2 | |||
MYH7 | NM_001407004.1 | c.2286+7A>G | splice_region_variant, intron_variant | NP_001393933.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.2286+7A>G | splice_region_variant, intron_variant | 1 | NM_000257.4 | ENSP00000347507 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251176Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135742
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461662Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727142
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 13, 2023 | Variant summary: MYH7 c.2286+7A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251176 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2286+7A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at