rs11538264

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.5320G>A(p.Val1774Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,614,168 control chromosomes in the GnomAD database, including 1,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.045 ( 271 hom., cov: 33)

Exomes 𝑓: 0.024 ( 891 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.22

Publications

21 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=0.0019162595).

BP6

Variant 6-31635412-G-A is Benign according to our data. Variant chr6-31635412-G-A is described in ClinVar as [Benign]. Clinvar id is 3057120.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.5320G>A	p.Val1774Met	missense_variant	Exon 23 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.5320G>A	p.Val1774Met	missense_variant	Exon 23 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.5320G>A	p.Val1774Met	missense_variant	Exon 23 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.5320G>A	p.Val1774Met	missense_variant	Exon 23 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6857

AN:

152246

Hom.:

268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0887

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0555

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0693

GnomAD2 exomes

AF:

0.0327

AC:

8221

AN:

251250

AF XY:

0.0299

show subpopulations

Gnomad AFR exome

AF:

0.0880

Gnomad AMR exome

AF:

0.0523

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0134

Gnomad FIN exome

AF:

0.00263

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0466

GnomAD4 exome

AF:

0.0238

AC:

34792

AN:

1461804

Hom.:

891

Cov.:

AF XY:

0.0236

AC XY:

17128

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0885

AC:

2964

AN:

33476

American (AMR)

AF:

0.0531

AC:

2376

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

3653

AN:

26128

East Asian (EAS)

AF:

0.0449

AC:

1782

AN:

39700

South Asian (SAS)

AF:

0.0163

AC:

1407

AN:

86256

European-Finnish (FIN)

AF:

0.00279

AC:

149

AN:

53420

Middle Eastern (MID)

AF:

0.0680

AC:

392

AN:

5768

European-Non Finnish (NFE)

AF:

0.0178

AC:

19841

AN:

1111940

Other (OTH)

AF:

0.0369

AC:

2228

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2088

4176

6265

8353

10441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0451

AC:

6876

AN:

152364

Hom.:

271

Cov.:

AF XY:

0.0439

AC XY:

3271

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0890

AC:

3700

AN:

41576

American (AMR)

AF:

0.0555

AC:

850

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

488

AN:

3472

East Asian (EAS)

AF:

0.0173

AC:

AN:

5192

South Asian (SAS)

AF:

0.0170

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0218

AC:

1480

AN:

68040

Other (OTH)

AF:

0.0686

AC:

145

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

321

643

964

1286

1607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0349

Hom.:

511

Bravo

AF:

0.0516

TwinsUK

AF:

0.0162

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.0850

AC:

257

ESP6500EA

AF:

0.0271

AC:

147

ExAC

AF:

0.0312

AC:

3791

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0282

EpiControl

AF:

0.0302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Jan 14, 2020

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

0.15

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;N

PhyloP100

1.2

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.073

Sift

Benign

0.045

D;D

Sift4G

Benign

0.086

T;T

Polyphen

0.0030

B;B

Vest4

0.12

MPC

0.16

ClinPred

0.0038

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.041

gMVP

0.22

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs11538264

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