rs2736158

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000376033.3(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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.066 ( 509 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1669 hom. )

Consequence

PRRC2A
ENST00000376033.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.64

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein
PRRC2A	NM_004638.4 linkuse as main transcript	c.3854G>C	p.Gly1285Ala	missense_variant	16/31	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3 linkuse as main transcript	c.3854G>C	p.Gly1285Ala	missense_variant	16/31		NP_542417.2
PRRC2A	XM_047419336.1 linkuse as main transcript	c.3854G>C	p.Gly1285Ala	missense_variant	16/30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 linkuse as main transcript	c.3854G>C	p.Gly1285Ala	missense_variant	16/31	1	NM_004638.4	ENSP00000365201	P1	P48634-1
PRRC2A	ENST00000376007.8 linkuse as main transcript	c.3854G>C	p.Gly1285Ala	missense_variant	16/31	1		ENSP00000365175	P1	P48634-1

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

GnomAD3 exomes

AF:

0.0489

AC:

11941

AN:

244426

Hom.:

583

AF XY:

0.0473

AC XY:

6305

AN XY:

133188

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 SAS exome

AF:

0.0546

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

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.0541

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.0977

Gnomad4 SAS exome

AF:

0.0541

Gnomad4 FIN exome

AF:

0.00608

Gnomad4 NFE exome

AF:

0.0298

Gnomad4 OTH exome

AF:

0.0511

GnomAD4 genome

AF:

0.0662

AC:

10074

AN:

152184

Hom.:

509

Cov.:

AF XY:

0.0663

AC XY:

4928

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.0613

Gnomad4 ASJ

AF:

0.0498

Gnomad4 EAS

AF:

0.131

Gnomad4 SAS

AF:

0.0597

Gnomad4 FIN

AF:

0.00585

Gnomad4 NFE

AF:

0.0288

Gnomad4 OTH

AF:

0.0721

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 2019

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

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

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

MutationTaster

Benign

1.0

P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over