1-228158026-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_StrongPP5
The NM_020435.4(GJC2):c.268C>T(p.Pro90Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,611,020 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 Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
GJC2
NM_020435.4 missense
NM_020435.4 missense
Scores
15
2
2
Clinical Significance
Conservation
PhyloP100: 5.91
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 5 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993
PP5
Variant 1-228158026-C-T is Pathogenic according to our data. Variant chr1-228158026-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2072.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-228158026-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.268C>T | p.Pro90Ser | missense_variant | 2/2 | ENST00000366714.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJC2 | ENST00000366714.3 | c.268C>T | p.Pro90Ser | missense_variant | 2/2 | 1 | NM_020435.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151722Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000412 AC: 1AN: 242738Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132604
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1459298Hom.: 0 Cov.: 37 AF XY: 0.0000193 AC XY: 14AN XY: 725960
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151722Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74104
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypomyelinating leukodystrophy 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at P90 (P = 0.0069);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at