2-208128309-C-CG
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_020989.4(CRYGC):c.418_419insC(p.Arg140ProfsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
CRYGC
NM_020989.4 frameshift
NM_020989.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.20
Genes affected
CRYGC (HGNC:2410): (crystallin gamma C) This gene encodes a member of the beta/gamma-crystallin family of proteins. Crystallins constitute the major proteins of vertebrate eye lens and maintain the transparency and refractive index of the lens. This gene and several family members are present in a gene cluster on chromosome 2. Mutations in this gene have been shown to cause multiple types of cataract, including Coppock-like cataract and zonular pulverulent cataract, among others. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 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 4 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-208128309-C-CG is Pathogenic according to our data. Variant chr2-208128309-C-CG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1475373.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRYGC | NM_020989.4 | c.418_419insC | p.Arg140ProfsTer24 | frameshift_variant | 3/3 | ENST00000282141.4 | NP_066269.1 | |
LOC100507443 | NR_038437.1 | n.98-8745dup | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRYGC | ENST00000282141.4 | c.418_419insC | p.Arg140ProfsTer24 | frameshift_variant | 3/3 | 1 | NM_020989.4 | ENSP00000282141 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nuclear pulverulent cataract Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 12, 2021 | This premature translational stop signal has been observed in individual(s) with congenital cataract (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg140Profs*24) in the CRYGC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the CRYGC protein. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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
Publications
No publications associated with this variant yet.