7-16801149-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_006408.4(AGR2):c.256+2T>C variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006408.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGR2 | NM_006408.4 | c.256+2T>C | splice_donor_variant | ENST00000419304.7 | |||
AGR2 | XM_005249581.5 | c.256+2T>C | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGR2 | ENST00000419304.7 | c.256+2T>C | splice_donor_variant | 1 | NM_006408.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000799 AC: 2AN: 250412Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135378
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1460570Hom.: 0 Cov.: 30 AF XY: 0.0000234 AC XY: 17AN XY: 726614
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74394
ClinVar
Submissions by phenotype
Respiratory infections, recurrent, and failure to thrive with or without diarrhea Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | May 12, 2023 | The AGR2 c.256+2T>C variant is classified as Likely Pathogenic (PVS1, PM2) The AGR2 c.256+2T>C variant is located in the exon 4 splice donor region. Computational predictions support a deleterious effect on splicing and a likely disruption of the protein reading frame (PVS1). The variant is rare in population databases (gnomAD allele frequency = 0.00065%; 1 het and 0 hom in 152,264 sequenced alleles) (PM2). The variant has been reported in dbSNP (rs753915618). It has not been reported in ClinVar, HGMD or the scientific literature to date. - |
AGR2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 16, 2024 | The AGR2 c.256+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature This variant is reported in 0.0018% 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