21-44113785-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_005049.3(PWP2):c.164G>A(p.Arg55Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 0)
Exomes 𝑓: 0.000020 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PWP2
NM_005049.3 missense
NM_005049.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 1.79
Genes affected
PWP2 (HGNC:9711): (PWP2 small subunit processome component) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and ribosomal small subunit assembly. Predicted to be located in nucleoplasm. Predicted to be part of Pwp2p-containing subcomplex of 90S preribosome and small-subunit processome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.087414235).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PWP2 | NM_005049.3 | c.164G>A | p.Arg55Gln | missense_variant | 3/21 | ENST00000291576.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PWP2 | ENST00000291576.12 | c.164G>A | p.Arg55Gln | missense_variant | 3/21 | 1 | NM_005049.3 | P1 | |
PWP2 | ENST00000456705.1 | c.164G>A | p.Arg55Gln | missense_variant | 3/6 | 3 |
Frequencies
GnomAD3 genomes Cov.: 0
GnomAD3 genomes
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0
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250966Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135812
GnomAD3 exomes
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000199 AC: 1AN: 50178Hom.: 0 Cov.: 0 AF XY: 0.0000372 AC XY: 1AN XY: 26914
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome Cov.: 0
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0
ESP6500AA
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3
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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 | Mar 29, 2022 | The c.164G>A (p.R55Q) alteration is located in exon 3 (coding exon 3) of the PWP2 gene. This alteration results from a G to A substitution at nucleotide position 164, causing the arginine (R) at amino acid position 55 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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