rs587776888
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PM2PP5_Very_StrongBP4
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 Pathogenic (★★).
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
Unknown
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.233
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ACMG classification
Verdict is Likely_pathogenic. Variant got 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]. Clinvar id 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.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
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Frequencies
GnomAD3 genomes Cov.: 34
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:
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0
AN:
188
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Cov.:
0
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AC XY:
0
AN XY:
140
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hypomyelinating leukodystrophy 2 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2012 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Spastic paraplegia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects GJC2 function (PMID: 20695017, 21246605, 24374284). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 30759). This variant has been observed in individual(s) with Pelizaeus–Merzbacher-like disease (PMID: 20695017, 21246605, 21959080, 23142375). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the GJC2 gene. It does not change the encoded amino acid sequence of the GJC2 protein. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 10, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Calibrated prediction
Score
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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