chr3-38138670-CGACCGCGCTGAGGCTCCAG-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_002468.5(MYD88):c.-24_-6delGCTGAGGCTCCAGGACCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,561,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002468.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000296 AC: 45AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000364 AC: 75AN: 206006Hom.: 0 AF XY: 0.000360 AC XY: 41AN XY: 113806
GnomAD4 exome AF: 0.000578 AC: 814AN: 1409132Hom.: 0 AF XY: 0.000540 AC XY: 375AN XY: 694786
GnomAD4 genome AF: 0.000296 AC: 45AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74374
ClinVar
Submissions by phenotype
Pyogenic bacterial infections due to MyD88 deficiency Pathogenic:1Uncertain:1
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This sequence change creates a premature translational stop signal (p.Ala6Profs*39) in the MYD88 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYD88 are known to be pathogenic (PMID: 18669862, 20538326). This variant is present in population databases (rs746651350, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MYD88-related conditions. ClinVar contains an entry for this variant (Variation ID: 469578). For these reasons, this variant has been classified as Pathogenic. -
MYD88-related disorder Uncertain:1
The MYD88 c.16_34del19 variant is predicted to result in a frameshift and premature protein termination (p.Ala6Profs*39). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.061% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be causative of disease. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at