chr2-177392835-G-GGCGCGA
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_003659.4(AGPS):c.49_54dupGCGAGC(p.Ala17_Ser18dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000064 in 1,548,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003659.4 conservative_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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AGPS | NM_003659.4 | c.49_54dupGCGAGC | p.Ala17_Ser18dup | conservative_inframe_insertion | Exon 1 of 20 | ENST00000264167.11 | NP_003650.1 | |
AGPS | XM_047446105.1 | c.49_54dupGCGAGC | p.Ala17_Ser18dup | conservative_inframe_insertion | Exon 1 of 10 | XP_047302061.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151944Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000167 AC: 24AN: 144012Hom.: 0 AF XY: 0.000201 AC XY: 16AN XY: 79754
GnomAD4 exome AF: 0.0000680 AC: 95AN: 1396086Hom.: 0 Cov.: 32 AF XY: 0.000100 AC XY: 69AN XY: 690202
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151944Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74232
ClinVar
Submissions by phenotype
not provided Uncertain:2
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This variant, c.49_54dup, results in the insertion of 2 amino acid(s) of the AGPS protein (p.Ala17_Ser18dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs771730798, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with AGPS-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
not specified Uncertain:1
Variant summary: AGPS c.49_54dupGCGAGC (p.Ala17_Ser18dup) results in an in-frame duplication that is predicted to duplicate 2 amino acids into the encoded protein. The variant allele was found at a frequency of 0.00017 in 144012 control chromosomes, predominantly at a frequency of 0.00098 within the South Asian subpopulation in the gnomAD database. This frequency is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in AGPS causing Rhizomelic Chondrodysplasia Punctata (0.00098 vs 0.0011). To our knowledge, no occurrence of c.49_54dupGCGAGC in individuals affected with Rhizomelic Chondrodysplasia Punctata and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at