rs746050475
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_020435.4(GJC2):βc.469_474delβ(p.Glu157_Glu158del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 1,479,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.000033 ( 0 hom., cov: 32)
Exomes π: 0.000027 ( 0 hom. )
Consequence
GJC2
NM_020435.4 inframe_deletion
NM_020435.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.06
Genes affected
GJC2 (HGNC:17494): (gap junction protein gamma 2) This gene encodes a gap junction protein. Gap junction proteins are members of a large family of homologous connexins and comprise 4 transmembrane, 2 extracellular, and 3 cytoplasmic domains. This gene plays a key role in central myelination and is involved in peripheral myelination in humans. Defects in this gene are the cause of autosomal recessive Pelizaeus-Merzbacher-like disease-1. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.469_474del | p.Glu157_Glu158del | inframe_deletion | 2/2 | ENST00000366714.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJC2 | ENST00000366714.3 | c.469_474del | p.Glu157_Glu158del | inframe_deletion | 2/2 | 1 | NM_020435.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000333 AC: 5AN: 150104Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000271 AC: 36AN: 1329472Hom.: 0 AF XY: 0.0000323 AC XY: 21AN XY: 650792
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GnomAD4 genome ? AF: 0.0000333 AC: 5AN: 150182Hom.: 0 Cov.: 32 AF XY: 0.0000546 AC XY: 4AN XY: 73306
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 28, 2021 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with GJC2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.469_474del, results in the deletion of 2 amino acid(s) of the GJC2 protein (p.Glu157_Glu158del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at