chr15-23644041-G-GTCA
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_019066.5(MAGEL2):c.3699_3701dupTGA(p.Asp1234dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,612,062 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_019066.5 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 247970Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134482
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1459864Hom.: 0 Cov.: 32 AF XY: 0.0000262 AC XY: 19AN XY: 725894
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
The MAGEL2 p.Asp1234dup variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs779843667) and in control databases in 4 of 247970 chromosomes at a frequency of 0.00001613 (Genome Aggregation Database March 6, 2019, v2.1.1). This variant is an in-frame insertion resulting in the duplication of an aspartic acid (asp) residue at codon 1234; the impact of this alteration on MAGEL2 protein function is not known. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
MAGEL2-related disorder Uncertain:1
The MAGEL2 c.3699_3701dupTGA variant is predicted to result in an in-frame duplication (p.Asp1234dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0036% of alleles in individuals of European (Non-Finnish) descent in gnomAD. 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