rs2736158

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004638.4(PRRC2A):c.3854G>C(p.Gly1285Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 1,609,644 control chromosomes in the GnomAD database, including 2,178 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.066 ( 509 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1669 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.64

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016219318).

BP6

Variant 6-31632527-G-C is Benign according to our data. Variant chr6-31632527-G-C is described in ClinVar as Benign. ClinVar VariationId is 1229769.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PRRC2A	NM_004638.4 link	c.3854G>C	p.Gly1285Ala	missense_variant	Exon 16 of 31	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3 link	c.3854G>C	p.Gly1285Ala	missense_variant	Exon 16 of 31		NP_542417.2
PRRC2A	XM_047419336.1 link	c.3854G>C	p.Gly1285Ala	missense_variant	Exon 16 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.3854G>C	p.Gly1285Ala	missense_variant	Exon 16 of 31	1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8 link	c.3854G>C	p.Gly1285Ala	missense_variant	Exon 16 of 31	1		ENSP00000365175.4

Frequencies

GnomAD3 genomes

AF:

0.0662

AC:

10070

AN:

152066

Hom.:

509

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.0498

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.0599

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.0724

GnomAD2 exomes

AF:

0.0489

AC:

11941

AN:

244426

AF XY:

0.0473

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0517

Gnomad ASJ exome

AF:

0.0488

Gnomad EAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.00464

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0473

GnomAD4 exome

AF:

0.0373

AC:

54378

AN:

1457460

Hom.:

1669

Cov.:

AF XY:

0.0374

AC XY:

27084

AN XY:

724604

show subpopulations

African (AFR)

AF:

0.146

AC:

4882

AN:

33420

American (AMR)

AF:

0.0541

AC:

2411

AN:

44554

Ashkenazi Jewish (ASJ)

AF:

0.0512

AC:

1327

AN:

25930

East Asian (EAS)

AF:

0.0977

AC:

3874

AN:

39640

South Asian (SAS)

AF:

0.0541

AC:

4651

AN:

86022

European-Finnish (FIN)

AF:

0.00608

AC:

317

AN:

52130

Middle Eastern (MID)

AF:

0.130

AC:

749

AN:

5750

European-Non Finnish (NFE)

AF:

0.0298

AC:

33092

AN:

1109806

Other (OTH)

AF:

0.0511

AC:

3075

AN:

60208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

3488

6977

10465

13954

17442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1466

2932

4398

5864

7330

<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:

0.0662

AC:

10074

AN:

152184

Hom.:

509

Cov.:

AF XY:

0.0663

AC XY:

4928

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.139

AC:

5778

AN:

41520

American (AMR)

AF:

0.0613

AC:

937

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0498

AC:

173

AN:

3472

East Asian (EAS)

AF:

0.131

AC:

677

AN:

5174

South Asian (SAS)

AF:

0.0597

AC:

288

AN:

4824

European-Finnish (FIN)

AF:

0.00585

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0288

AC:

1961

AN:

67998

Other (OTH)

AF:

0.0721

AC:

152

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

477

954

1431

1908

2385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0363

Hom.:

153

Bravo

AF:

0.0736

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0293

AC:

113

ESP6500AA

AF:

0.133

AC:

401

ESP6500EA

AF:

0.0297

AC:

161

ExAC

AF:

0.0482

AC:

5710

Asia WGS

AF:

0.0790

AC:

274

AN:

3478

EpiCase

AF:

0.0309

EpiControl

AF:

0.0319

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Feb 27, 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). -

not provided

Benign:1

Feb 18, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23221128) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0031

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.66

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.061

Sift

Benign

0.14

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.21

MPC

0.17

ClinPred

0.013

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over