chr17-38735267-GC-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007144.3(PCGF2):c.990del(p.Arg331AlafsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000341 in 1,466,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000030 ( 0 hom. )
Consequence
PCGF2
NM_007144.3 frameshift
NM_007144.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.178
Genes affected
PCGF2 (HGNC:12929): (polycomb group ring finger 2) The protein encoded by this gene contains a RING finger motif and is similar to the polycomb group (PcG) gene products. PcG gene products form complexes via protein-protein interaction and maintain the transcription repression of genes involved in embryogenesis, cell cycles, and tumorigenesis. This protein was shown to act as a negative regulator of transcription and has tumor suppressor activity. The expression of this gene was detected in various tumor cells, but is limited in neural organs in normal tissues. Knockout studies in mice suggested that this protein may negatively regulate the expression of different cytokines, chemokines, and chemokine receptors, and thus plays an important role in lymphocyte differentiation and migration, as well as in immune responses. [provided by RefSeq, Jul 2008]
CISD3 (HGNC:27578): (CDGSH iron sulfur domain 3) CISD3 is a member of the CDGSH domain-containing family, which may play a role in regulating electron transport and oxidative phosphorylation (Wiley et al., 2007 [PubMed 17376863]).[supplied by OMIM, Apr 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCGF2 | NM_007144.3 | c.990del | p.Arg331AlafsTer3 | frameshift_variant | 11/11 | ENST00000620225.5 | |
CISD3 | NM_001136498.2 | c.*1817del | 3_prime_UTR_variant | 4/4 | ENST00000613478.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCGF2 | ENST00000620225.5 | c.990del | p.Arg331AlafsTer3 | frameshift_variant | 11/11 | 1 | NM_007144.3 | P1 | |
CISD3 | ENST00000613478.2 | c.*1817del | 3_prime_UTR_variant | 4/4 | 2 | NM_001136498.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000304 AC: 4AN: 1314564Hom.: 0 Cov.: 33 AF XY: 0.00000313 AC XY: 2AN XY: 638170
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with PCGF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg331Alafs*3) in the PCGF2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acid(s) of the PCGF2 protein. - |
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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