chr1-228158211-C-CGAG
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_020435.4(GJC2):c.472_474dup(p.Glu158dup) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,480,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G151G) has been classified as Likely benign.
Frequency
Consequence
NM_020435.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.472_474dup | p.Glu158dup | inframe_insertion | 2/2 | ENST00000366714.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJC2 | ENST00000366714.3 | c.472_474dup | p.Glu158dup | inframe_insertion | 2/2 | 1 | NM_020435.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000733 AC: 11AN: 150110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000335 AC: 14AN: 41820Hom.: 0 AF XY: 0.000309 AC XY: 7AN XY: 22658
GnomAD4 exome AF: 0.000145 AC: 193AN: 1329974Hom.: 0 Cov.: 35 AF XY: 0.000135 AC XY: 88AN XY: 651122
GnomAD4 genome AF: 0.0000732 AC: 11AN: 150188Hom.: 0 Cov.: 32 AF XY: 0.0000818 AC XY: 6AN XY: 73312
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2023 | This variant, c.472_474dup, results in the insertion of 1 amino acid(s) of the GJC2 protein (p.Glu158dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with GJC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 241297). 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. - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at