X-21839750-C-CTGGTGG
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3
The NM_015884.4(MBTPS2):c.29_34dup(p.Val10_Val11dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000000928 in 1,077,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.
Frequency
Consequence
NM_015884.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MBTPS2 | NM_015884.4 | c.29_34dup | p.Val10_Val11dup | inframe_insertion | 1/11 | ENST00000379484.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MBTPS2 | ENST00000379484.10 | c.29_34dup | p.Val10_Val11dup | inframe_insertion | 1/11 | 1 | NM_015884.4 | P1 | |
MBTPS2 | ENST00000365779.2 | c.29_34dup | p.Val10_Val11dup | inframe_insertion | 1/7 | 1 | |||
MBTPS2 | ENST00000465888.1 | n.128_133dup | non_coding_transcript_exon_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 9.28e-7 AC: 1AN: 1077163Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 350855
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with MBTPS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.29_34dup, results in the insertion of 2 amino acid(s) of the MBTPS2 protein (p.Val10_Val11dup), but otherwise preserves the integrity of the reading frame. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In-frame insertion of 2 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.