ENST00000646873.1:c.312-12235G>A

Variant names:

• chr21-44128107-C-A
• NM_005049.3:c.2316C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005049.3(PWP2):​c.2316C>A​(p.Ser772Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PWP2 NM_005049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053866982).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005049.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWP2	NM_005049.3	MANE Select	c.2316C>A	p.Ser772Arg	missense	Exon 18 of 21	NP_005040.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PWP2	ENST00000291576.12	TSL:1 MANE Select	c.2316C>A	p.Ser772Arg	missense	Exon 18 of 21	ENSP00000291576.6	Q15269
	PWP2	ENST00000862525.1		c.2334C>A	p.Ser778Arg	missense	Exon 18 of 21	ENSP00000532584.1
	PWP2	ENST00000862526.1		c.2316C>A	p.Ser772Arg	missense	Exon 18 of 21	ENSP00000532585.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	N
PhyloP100		0.64
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.071
Sift	Benign	0.41	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.39		Gain of MoRF binding (P = 0.0152)
MVP		0.15
MPC		0.18
ClinPred		0.034	T
GERP RS		2.5
Varity_R		0.034
gMVP		0.23
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

hg19: chr21-45547988;