chr17-75592082-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001395058.1(MYO15B):c.2651+2T>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000427 in 702,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001395058.1 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15B | NM_001395058.1 | c.2651+2T>A | splice_donor_variant, intron_variant | Intron 6 of 63 | ENST00000645453.3 | NP_001381987.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO15B | ENST00000645453.3 | c.2651+2T>A | splice_donor_variant, intron_variant | Intron 6 of 63 | NM_001395058.1 | ENSP00000495242.3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000363 AC: 2AN: 550528Hom.: 0 Cov.: 0 AF XY: 0.00000336 AC XY: 1AN XY: 298042
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
Congenital myopathy Uncertain:1
The heterozygous c.2651+2T>A variant in MYO15B was identified by our study in 1 individual with dysphagia, ptosis, increased muscle fatigability, and muscle weakness. This variant was detected in cis with another variant of uncertain significance (p.Asp2703Glu) in MYO15B. While this gene is still lacking sufficient evidence to establish a gene-disease relationship, we believe this is a possible novel gene candidate for this phenotype. Given the limited information about this gene-disease relationship, the significance of the c.2651+2T>A variant is uncertain. If you have any additional information about functional evidence or other individuals with this phenotype that also have variants in MYO15B we encourage you to reach out to us. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at