rs2020945

Variant names:

• chr21-44109038-G-A
• rs2020945
• NM_005049.3:c.73G>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.73G>A​(p.Asp25Asn) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D25G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 9)
• Consequence: PWP2 NM_005049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• Publications: 49 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=2.3400784E-4).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PWP2	NM_005049.3	c.73G>A	p.Asp25Asn	missense_variant	Exon 2 of 21	ENST00000291576.12	NP_005040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PWP2	ENST00000291576.12	c.73G>A	p.Asp25Asn	missense_variant	Exon 2 of 21	1	NM_005049.3	ENSP00000291576.6
PWP2	ENST00000456705.1	c.73G>A	p.Asp25Asn	missense_variant	Exon 2 of 6	3		ENSP00000411749.1

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD2 exomes AF: 0.724 AC: 181913 AN: 251288 AF XY: 0.729

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.706

Gnomad FIN exome AF: 0.844

Gnomad NFE exome AF: 0.814

Gnomad OTH exome AF: 0.757

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 9

Alfa AF: 0.749 Hom.: 148677

TwinsUK AF: 0.800 AC: 2968

ALSPAC AF: 0.805 AC: 3101

ESP6500AA AF: 0.323 AC: 1425

ESP6500EA AF: 0.808 AC: 6948

ExAC AF: 0.715 AC: 86839

Asia WGS AF: 0.603 AC: 2100 AN: 3478

EpiCase AF: 0.815

EpiControl AF: 0.811

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	0.016
Eigen_PC	Benign	0.044
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T;D
MetaRNN	Benign	0.00023	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PhyloP100		7.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.23
Sift	Benign	0.074	T;D
Sift4G	Uncertain	0.056	T;T
Polyphen		0.70	P;.
Vest4		0.28
MPC		0.22
ClinPred		0.095	T
GERP RS		3.9
Varity_R		0.32
gMVP		0.80
Mutation Taster		=97/3	polymorphism (auto)

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

dbSNP: rs2020945; hg19: chr21-45528919; COSMIC: COSV52378282; COSMIC: COSV52378282;