Variant chr5-160093106-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001130864.2(PWWP2A):c.1544C>T(p.Ser515Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PWWP2A
NM_001130864.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.78

Variant links:

Genes affected

PWWP2A (HGNC:29406): (PWWP domain containing 2A) Enables chromatin binding activity and histone binding activity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PWWP2A links:

PWWP2A (HGNC:):

PWWP2A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41199654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PWWP2A	NM_001130864.2 linkuse as main transcript	c.1544C>T	p.Ser515Leu	missense_variant	2/2	ENST00000307063.9	NP_001124336.1	Q96N64-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PWWP2A	ENST00000307063.9 linkuse as main transcript	c.1544C>T	p.Ser515Leu	missense_variant	2/2	1	NM_001130864.2	ENSP00000305151.7		Q96N64-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248836

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135028

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461644

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jun 17, 2024

The c.1544C>T (p.S515L) alteration is located in exon 2 (coding exon 2) of the PWWP2A gene. This alteration results from a C to T substitution at nucleotide position 1544, causing the serine (S) at amino acid position 515 to be replaced by a leucine (L). 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

0.19

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

.;.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.060

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.97

L;L;L

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;D;T

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.60

MutPred

0.15

Loss of phosphorylation at S515 (P = 0.004);Loss of phosphorylation at S515 (P = 0.004);Loss of phosphorylation at S515 (P = 0.004);

MVP

0.20

MPC

1.6

ClinPred

0.52

GERP RS

5.7

Varity_R

0.096

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over