chr19-14743419-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_ModerateBS2
The NM_013447.4(ADGRE2):c.2463+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000374 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013447.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRE2 | NM_013447.4 | c.2463+1G>A | splice_donor_variant | ENST00000315576.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRE2 | ENST00000315576.8 | c.2463+1G>A | splice_donor_variant | 1 | NM_013447.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000381 AC: 58AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000275 AC: 69AN: 251188Hom.: 0 AF XY: 0.000295 AC XY: 40AN XY: 135708
GnomAD4 exome AF: 0.000373 AC: 545AN: 1461176Hom.: 0 Cov.: 31 AF XY: 0.000367 AC XY: 267AN XY: 726956
GnomAD4 genome AF: 0.000381 AC: 58AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | This sequence change affects a donor splice site in intron 20 of the ADGRE2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ADGRE2 cause disease. This variant is present in population databases (rs141741521, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ADGRE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2079167). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at