Genetic Variant NM_001130864.2:c.2232C>T (chr5-160092418-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130864.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PWWP2A	NM_001130864.2	MANE Select	c.2232C>T	p.Pro744Pro	synonymous	Exon 2 of 2	NP_001124336.1	Q96N64-1
PWWP2A	NM_001349732.2		c.1581C>T	p.Pro527Pro	synonymous	Exon 4 of 4	NP_001336661.1
PWWP2A	NM_052927.4		c.1549+683C>T		intron	N/A	NP_443159.1	Q96N64-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PWWP2A	ENST00000307063.9	TSL:1 MANE Select	c.2232C>T	p.Pro744Pro	synonymous	Exon 2 of 2	ENSP00000305151.7	Q96N64-1
PWWP2A	ENST00000456329.7	TSL:1	c.1549+683C>T		intron	N/A	ENSP00000390462.2	Q96N64-2
PWWP2A	ENST00000523662.1	TSL:1	c.1549+683C>T		intron	N/A	ENSP00000428143.1	Q96N64-3

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

GnomAD2 exomes

AF:

0.00296

AC:

451

AN:

152262

AF XY:

0.00277

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 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

African (AFR)

AF:

0.0000960

AC:

AN:

31250

American (AMR)

AF:

0.000229

AC:

AN:

34950

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

25054

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35728

South Asian (SAS)

AF:

0.000986

AC:

AN:

79134

European-Finnish (FIN)

AF:

0.0119

AC:

585

AN:

49250

Middle Eastern (MID)

AF:

0.000529

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00282

AC:

3042

AN:

1078314

Other (OTH)

AF:

0.00270

AC:

156

AN:

57814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00303

AC:

462

AN:

152242

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41550

American (AMR)

AF:

0.000458

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00933

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00473

AC:

322

AN:

68022

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00435

Hom.:

Bravo

AF:

0.00200

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

(source)

DANN

Benign

0.48

PhyloP100

-0.73

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over