1-228157737-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_020435.4(GJC2):c.-19-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 683,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020435.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.-19-3C>A | splice_region_variant, intron_variant | ENST00000366714.3 | NP_065168.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GJC2 | ENST00000366714.3 | c.-19-3C>A | splice_region_variant, intron_variant | 1 | NM_020435.4 | ENSP00000355675.2 |
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151178Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000169 AC: 9AN: 531898Hom.: 0 Cov.: 10 AF XY: 0.0000105 AC XY: 3AN XY: 286752
GnomAD4 genome AF: 0.00000661 AC: 1AN: 151178Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1AN XY: 73752
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 02, 2018 | A variant of uncertain significance has been identified in the GJC2 gene. The c.-19-3 C>A variant hasnot been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). Several in silico splice prediction models predict that c.-19-3 C>A destroys a natural splice acceptor site in intron 1 which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at