21-44114759-A-C

Position:

• chr21-44114759-A-C

Variant summary

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

The NM_005049.3(PWP2):​c.461A>C​(p.Asp154Ala) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: PWP2 NM_005049.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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	Protein	UniProt
PWP2	NM_005049.3	c.461A>C	p.Asp154Ala	missense_variant	5/21	ENST00000291576.12	NP_005040.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PWP2	ENST00000291576.12	c.461A>C	p.Asp154Ala	missense_variant	5/21	1	NM_005049.3	ENSP00000291576.6
PWP2	ENST00000456705.1	c.361A>C	p.Met121Leu	missense_variant	4/6	3		ENSP00000411749.1
PWP2	ENST00000486126.1	n.184A>C		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

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

Jun 10, 2024

The c.461A>C (p.D154A) alteration is located in exon 5 (coding exon 5) of the PWP2 gene. This alteration results from a A to C substitution at nucleotide position 461, causing the aspartic acid (D) at amino acid position 154 to be replaced by an alanine (A). 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	Benign	0.15
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.089
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.20
Sift	Benign	0.59	T
Sift4G	Benign	0.64	T
Polyphen		0.72	P
Vest4		0.66
MutPred		0.48		Gain of catalytic residue at S156 (P = 0.1551);
MVP		0.56
MPC		0.27
ClinPred		0.64	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-45534640;