chr21-44108995-G-C

Position:

• chr21-44108995-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_005049.3(PWP2):​c.30G>C​(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 7)
• Consequence: PWP2 NM_005049.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PWP2	NM_005049.3	c.30G>C	p.Leu10Phe	missense_variant	2/21	ENST00000291576.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PWP2	ENST00000291576.12	c.30G>C	p.Leu10Phe	missense_variant	2/21	1	NM_005049.3	P1
PWP2	ENST00000456705.1	c.30G>C	p.Leu10Phe	missense_variant	2/6	3

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.30G>C (p.L10F) alteration is located in exon 2 (coding exon 2) of the PWP2 gene. This alteration results from a G to C substitution at nucleotide position 30, causing the leucine (L) at amino acid position 10 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.012	D
MutationAssessor	Pathogenic	3.1	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.68
MutPred		0.58		Gain of MoRF binding (P = 0.1142);Gain of MoRF binding (P = 0.1142);
MVP		0.71
MPC		0.72
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.34
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs773881408; hg19: chr21-45528876;