Genetic Variant PWWP2A:p.Pro744Pro (chr5-160092418-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001130864.2(PWWP2A):c.2232C>T(p.Pro744Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,549,406 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 24 hom. )

Consequence

PWWP2A
NM_001130864.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.732

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-160092418-G-A is Benign according to our data. Variant chr5-160092418-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656009.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.732 with no splicing effect.

BS2

High AC in GnomAd4 at 462 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PWWP2A	NM_001130864.2 link	c.2232C>T	p.Pro744Pro	synonymous_variant	Exon 2 of 2	ENST00000307063.9	NP_001124336.1	Q96N64-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PWWP2A	ENST00000307063.9 link	c.2232C>T	p.Pro744Pro	synonymous_variant	Exon 2 of 2	1	NM_001130864.2	ENSP00000305151.7		Q96N64-1

Frequencies

GnomAD3 genomes

AF:

0.00304

AC:

462

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00933

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00473

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00296

AC:

451

AN:

152262

Hom.:

AF XY:

0.00277

AC XY:

224

AN XY:

80922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00371

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000706

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.00393

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.00284

AC:

3970

AN:

1397164

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

2029

AN XY:

689260

show subpopulations

Gnomad4 AFR exome

AF:

0.0000960

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00303

AC:

462

AN:

152242

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00933

Gnomad4 NFE

AF:

0.00473

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.00200

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PWWP2A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

DANN

Benign

0.48

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