rs587776888
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
The NM_020435.4(GJC2):c.-167A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GJC2
NM_020435.4 upstream_gene
NM_020435.4 upstream_gene
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.233
Publications
8 publications found
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]
GJC2 Gene-Disease associations (from GenCC):
- hypomyelinating leukodystrophy 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
- lymphatic malformation 3Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- hereditary spastic paraplegia 44Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- lymphatic malformationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-228149860-A-G is Pathogenic according to our data. Variant chr1-228149860-A-G is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 30759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4). . Strength limited to SUPPORTING due to the PP5.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_020435.4. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 188Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 140
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
188
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
140
African (AFR)
AF:
AC:
0
AN:
2
American (AMR)
AF:
AC:
0
AN:
2
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AF:
AC:
0
AN:
2
South Asian (SAS)
AF:
AC:
0
AN:
18
European-Finnish (FIN)
AF:
AC:
0
AN:
2
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
AC:
0
AN:
160
Other (OTH)
AF:
AC:
0
AN:
2
GnomAD4 genome
GnomAD4 genome
Cov.:
34
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Hypomyelinating leukodystrophy 2 (3)
1
-
-
Hereditary spastic paraplegia 44 (1)
1
-
-
not provided (1)
1
-
-
Spastic paraplegia (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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