rs878853083
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020435.4(GJC2):c.17G>A(p.Trp6Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000295 in 1,015,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000016 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000011 ( 0 hom. )
Consequence
GJC2
NM_020435.4 stop_gained
NM_020435.4 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 9.63
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 53 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-228157775-G-A is Pathogenic according to our data. Variant chr1-228157775-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 235629.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.17G>A | p.Trp6Ter | stop_gained | 2/2 | ENST00000366714.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJC2 | ENST00000366714.3 | c.17G>A | p.Trp6Ter | stop_gained | 2/2 | 1 | NM_020435.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000165 AC: 2AN: 121398Hom.: 0 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
2
AN:
121398
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000112 AC: 1AN: 893988Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 442100
GnomAD4 exome
AF:
AC:
1
AN:
893988
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
442100
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000165 AC: 2AN: 121398Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 56136
GnomAD4 genome
?
AF:
AC:
2
AN:
121398
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
56136
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 11, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at