rs1046089

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004638.4(PRRC2A):c.5219G>A(p.Arg1740His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,613,872 control chromosomes in the GnomAD database, including 106,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.40 ( 12571 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93991 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.41

Publications

123 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.2975626E-4).

BP6

Variant 6-31635190-G-A is Benign according to our data. Variant chr6-31635190-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060262.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.5219G>A	p.Arg1740His	missense_variant	Exon 22 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.5219G>A	p.Arg1740His	missense_variant	Exon 22 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.5219G>A	p.Arg1740His	missense_variant	Exon 22 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.5219G>A	p.Arg1740His	missense_variant	Exon 22 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60663

AN:

151920

Hom.:

12565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.366

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.360

GnomAD2 exomes

AF:

0.357

AC:

89663

AN:

251378

AF XY:

0.346

show subpopulations

Gnomad AFR exome

AF:

0.513

Gnomad AMR exome

AF:

0.383

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.476

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.354

AC:

517868

AN:

1461834

Hom.:

93991

Cov.:

AF XY:

0.349

AC XY:

253786

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.514

AC:

17198

AN:

33476

American (AMR)

AF:

0.380

AC:

16985

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

5276

AN:

26134

East Asian (EAS)

AF:

0.369

AC:

14645

AN:

39700

South Asian (SAS)

AF:

0.272

AC:

23443

AN:

86252

European-Finnish (FIN)

AF:

0.476

AC:

25442

AN:

53420

Middle Eastern (MID)

AF:

0.288

AC:

1661

AN:

5766

European-Non Finnish (NFE)

AF:

0.353

AC:

392135

AN:

1111974

Other (OTH)

AF:

0.349

AC:

21083

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

22151

44303

66454

88606

110757

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12672

25344

38016

50688

63360

<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:

0.399

AC:

60700

AN:

152038

Hom.:

12571

Cov.:

AF XY:

0.402

AC XY:

29892

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.503

AC:

20848

AN:

41476

American (AMR)

AF:

0.367

AC:

5607

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3468

East Asian (EAS)

AF:

0.366

AC:

1884

AN:

5150

South Asian (SAS)

AF:

0.293

AC:

1411

AN:

4818

European-Finnish (FIN)

AF:

0.499

AC:

5263

AN:

10556

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.351

AC:

23849

AN:

67966

Other (OTH)

AF:

0.359

AC:

760

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1855

3710

5565

7420

9275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.364

Hom.:

46320

Bravo

AF:

0.397

TwinsUK

AF:

0.351

AC:

1300

ALSPAC

AF:

0.348

AC:

1343

ESP6500AA

AF:

0.510

AC:

2245

ESP6500EA

AF:

0.345

AC:

2971

ExAC

AF:

0.357

AC:

43360

Asia WGS

AF:

0.339

AC:

1178

AN:

3478

EpiCase

AF:

0.324

EpiControl

AF:

0.318

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.73

.;T

MetaRNN

Benign

0.00083

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.90

L;L

PhyloP100

3.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.053

T;T

Sift4G

Uncertain

0.029

D;D

Polyphen

0.96

D;D

Vest4

0.19

MPC

0.20

ClinPred

0.012

GERP RS

5.5

Varity_R

0.13

gMVP

0.35

Mutation Taster

=97/3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over