Genetic Variant PRRC2A:c.4319+51A>G (chr6-31633043-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004638.4(PRRC2A):c.4319+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,450,738 control chromosomes in the GnomAD database, including 24,793 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2379 hom., cov: 32)

Exomes 𝑓: 0.18 ( 22414 hom. )

Consequence

PRRC2A
NM_004638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.10

Publications

36 publications found

Variant links:

Genes affected

PRRC2A (HGNC:13918): (proline rich coiled-coil 2A) A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

PRRC2A 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 (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.4319+51A>G	intron_variant	Intron 16 of 30	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.4319+51A>G	intron_variant	Intron 16 of 30		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.4319+51A>G	intron_variant	Intron 16 of 29		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.4319+51A>G		intron_variant	Intron 16 of 30	1	NM_004638.4	ENSP00000365201.2		P48634-1
PRRC2A	ENST00000376007.8 link	c.4319+51A>G		intron_variant	Intron 16 of 30	1		ENSP00000365175.4		P48634-1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25664

AN:

151982

Hom.:

2379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.0987

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0788

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.150

GnomAD2 exomes

AF:

0.146

AC:

11244

AN:

76768

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.0857

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.0965

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.180

AC:

234154

AN:

1298638

Hom.:

22414

Cov.:

AF XY:

0.178

AC XY:

112494

AN XY:

631260

show subpopulations

African (AFR)

AF:

0.210

AC:

6001

AN:

28638

American (AMR)

AF:

0.0879

AC:

1925

AN:

21902

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

2374

AN:

19404

East Asian (EAS)

AF:

0.0409

AC:

1430

AN:

34984

South Asian (SAS)

AF:

0.118

AC:

7735

AN:

65552

European-Finnish (FIN)

AF:

0.162

AC:

5555

AN:

34342

Middle Eastern (MID)

AF:

0.0916

AC:

460

AN:

5020

European-Non Finnish (NFE)

AF:

0.193

AC:

199635

AN:

1034772

Other (OTH)

AF:

0.167

AC:

9039

AN:

54024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

10787

21575

32362

43150

53937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7312

14624

21936

29248

36560

<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:

0.169

AC:

25664

AN:

152100

Hom.:

2379

Cov.:

AF XY:

0.164

AC XY:

12218

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.193

AC:

8005

AN:

41476

American (AMR)

AF:

0.0983

AC:

1504

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3470

East Asian (EAS)

AF:

0.0794

AC:

411

AN:

5178

South Asian (SAS)

AF:

0.124

AC:

601

AN:

4830

European-Finnish (FIN)

AF:

0.162

AC:

1711

AN:

10578

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12511

AN:

67958

Other (OTH)

AF:

0.148

AC:

313

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1108

2216

3323

4431

5539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.183

Hom.:

7139

Bravo

AF:

0.166

Asia WGS

AF:

0.0950

AC:

331

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.27

(source)

DANN

Benign

0.32

PhyloP100

-3.1

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

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