Genetic Variant NM_014819.5:c.2113G>A (chr5-109337245-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014819.5(PJA2):c.2113G>A(p.Ala705Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,612,554 control chromosomes in the GnomAD database, including 54,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4816 hom., cov: 31)

Exomes 𝑓: 0.25 ( 50123 hom. )

Consequence

PJA2
NM_014819.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

34 publications found

Variant links:

Genes affected

PJA2 (HGNC:17481): (praja ring finger ubiquitin ligase 2) Enables protein kinase A catalytic subunit binding activity; protein kinase A regulatory subunit binding activity; and ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of macrophage activation; and regulation of signal transduction. Located in cytoplasm; intermediate filament cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PJA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7231032E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PJA2	NM_014819.5 link	c.2113G>A	p.Ala705Thr	missense_variant	Exon 10 of 10	ENST00000361189.7	NP_055634.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PJA2	ENST00000361189.7 link	c.2113G>A	p.Ala705Thr	missense_variant	Exon 10 of 10	1	NM_014819.5	ENSP00000354775.2		O43164-1
PJA2	ENST00000361557.5 link	c.2113G>A	p.Ala705Thr	missense_variant	Exon 10 of 10	2		ENSP00000355284.3		O43164-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35810

AN:

151656

Hom.:

4810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.341

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.276

AC:

69320

AN:

250916

AF XY:

0.278

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.288

Gnomad EAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.252

AC:

367541

AN:

1460780

Hom.:

50123

Cov.:

AF XY:

0.254

AC XY:

184412

AN XY:

726738

show subpopulations

African (AFR)

AF:

0.152

AC:

5098

AN:

33450

American (AMR)

AF:

0.263

AC:

11716

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7503

AN:

26116

East Asian (EAS)

AF:

0.622

AC:

24622

AN:

39610

South Asian (SAS)

AF:

0.317

AC:

27276

AN:

86132

European-Finnish (FIN)

AF:

0.258

AC:

13760

AN:

53378

Middle Eastern (MID)

AF:

0.206

AC:

1172

AN:

5686

European-Non Finnish (NFE)

AF:

0.234

AC:

260472

AN:

1111488

Other (OTH)

AF:

0.264

AC:

15922

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

12882

25765

38647

51530

64412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9088

18176

27264

36352

45440

<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:

0.236

AC:

35835

AN:

151774

Hom.:

4816

Cov.:

AF XY:

0.243

AC XY:

18030

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.158

AC:

6527

AN:

41358

American (AMR)

AF:

0.265

AC:

4048

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

974

AN:

3472

East Asian (EAS)

AF:

0.588

AC:

3033

AN:

5158

South Asian (SAS)

AF:

0.336

AC:

1621

AN:

4820

European-Finnish (FIN)

AF:

0.267

AC:

2799

AN:

10490

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15991

AN:

67914

Other (OTH)

AF:

0.225

AC:

474

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1308

2616

3924

5232

6540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.241

Hom.:

20307

Bravo

AF:

0.230

TwinsUK

AF:

0.230

AC:

852

ALSPAC

AF:

0.233

AC:

899

ESP6500AA

AF:

0.162

AC:

713

ESP6500EA

AF:

0.234

AC:

2016

ExAC

AF:

0.276

AC:

33456

Asia WGS

AF:

0.491

AC:

1705

AN:

3478

EpiCase

AF:

0.241

EpiControl

AF:

0.235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.63

.;T

MetaRNN

Benign

0.000017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PhyloP100

-0.010

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.063

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.0

B;B

Vest4

0.033

MPC

0.99

ClinPred

0.015

GERP RS

0.45

Varity_R

0.024

gMVP

0.33

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over