rs1555993038
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006031.6(PCNT):c.7126C>T(p.Gln2376Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,606 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_006031.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCNT | NM_006031.6 | c.7126C>T | p.Gln2376Ter | stop_gained | 32/47 | ENST00000359568.10 | |
PCNT | NM_001315529.2 | c.6772C>T | p.Gln2258Ter | stop_gained | 32/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCNT | ENST00000359568.10 | c.7126C>T | p.Gln2376Ter | stop_gained | 32/47 | 1 | NM_006031.6 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461606Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727092
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Microcephalic osteodysplastic primordial dwarfism type II Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 22, 2015 | The p.Gln2376X variant in PCNT has not been previously reported in the literatur e or in large population studies. This nonsense variant leads to a premature ter mination codon at position 2376, which is predicted to lead to a truncated or ab sent protein. Nonsense and other loss of function variants in PCNT are establish ed to be disease causing for microcephalic osteodysplastic primordial dwarfism t ype 2. In summary, this variant meets our criteria to be classified as pathogeni c for microcephalic osteodysplastic primordial dwarfism type 2 in an autosomal r ecessive manner based upon its predicted impact to the protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at