1-228158211-CGAGGAG-CGAG
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS1
The NM_020435.4(GJC2):c.472_474delGAG(p.Glu158del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00534 in 1,328,342 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020435.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.472_474delGAG | p.Glu158del | conservative_inframe_deletion | Exon 2 of 2 | ENST00000366714.3 | NP_065168.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000187 AC: 28AN: 149912Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00599 AC: 7063AN: 1178354Hom.: 0 AF XY: 0.00677 AC XY: 3866AN XY: 570674
GnomAD4 genome AF: 0.000187 AC: 28AN: 149988Hom.: 0 Cov.: 32 AF XY: 0.000219 AC XY: 16AN XY: 73200
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
This sequence change deletes 3 nucleotides from exon 2 of the GJC2 mRNA (c.472_474delGAG). This leads to the deletion of 1 amino acid residue in the GJC2 protein (p.Glu158del) but otherwise preserves the integrity of the reading frame. While this variant is present in population databases (rs746050475), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a GJC2-related disease. In summary, this is a rare single amino acid deletion with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. -
GJC2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at