chr1-233000385-G-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014801.4(PCNX2):c.5248C>T(p.Arg1750Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,612,228 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
PCNX2
NM_014801.4 missense
NM_014801.4 missense
Scores
9
9
1
Clinical Significance
Conservation
PhyloP100: 0.717
Genes affected
PCNX2 (HGNC:8736): (pecanex 2) This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas. [provided by RefSeq, Jun 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.957
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCNX2 | NM_014801.4 | c.5248C>T | p.Arg1750Trp | missense_variant | 30/34 | ENST00000258229.14 | NP_055616.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCNX2 | ENST00000258229.14 | c.5248C>T | p.Arg1750Trp | missense_variant | 30/34 | 5 | NM_014801.4 | ENSP00000258229 | A2 | |
PCNX2 | ENST00000344698.6 | c.1204C>T | p.Arg402Trp | missense_variant | 7/10 | 2 | ENSP00000340759 | P4 | ||
PCNX2 | ENST00000462233.5 | c.*587C>T | 3_prime_UTR_variant, NMD_transcript_variant | 16/20 | 2 | ENSP00000428488 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000283 AC: 7AN: 247512Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134226
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460028Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726142
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2021 | The c.5248C>T (p.R1750W) alteration is located in exon 30 (coding exon 30) of the PCNX2 gene. This alteration results from a C to T substitution at nucleotide position 5248, causing the arginine (R) at amino acid position 1750 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Uncertain
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0563);.;
MVP
MPC
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