6-31624305-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004638.4(PRRC2A):c.335C>A(p.Pro112Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000985 in 1,613,992 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.703

Publications

1 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:

ENSG00000289282 (HGNC:):

ENSG00000289282 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019969195).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.335C>A	p.Pro112Gln	missense_variant	Exon 4 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.335C>A	p.Pro112Gln	missense_variant	Exon 4 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.335C>A	p.Pro112Gln	missense_variant	Exon 4 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRRC2A	ENST00000376033.3 link	c.335C>A	p.Pro112Gln	missense_variant	Exon 4 of 31	1	NM_004638.4	ENSP00000365201.2	P48634-1
PRRC2A	ENST00000376007.8 link	c.335C>A	p.Pro112Gln	missense_variant	Exon 4 of 31	1		ENSP00000365175.4	P48634-1
ENSG00000289282	ENST00000687518.1 link	c.81C>A	p.Ala27Ala	synonymous_variant	Exon 2 of 5			ENSP00000509222.1	A0A8I5QKQ9
PRRC2A	ENST00000469577.5 link	n.180C>A		non_coding_transcript_exon_variant	Exon 2 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000905

AC:

226

AN:

249650

AF XY:

0.000991

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.000995

AC:

1455

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

733

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00218

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000568

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000601

AC:

AN:

53222

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00111

AC:

1233

AN:

1111986

Other (OTH)

AF:

0.000977

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

162

244

325

406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000886

AC:

135

AN:

152332

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41566

American (AMR)

AF:

0.000850

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00140

AC:

AN:

68034

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000832

Hom.:

Bravo

AF:

0.000914

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000923

AC:

ExAC

AF:

0.000939

AC:

114

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 26, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.335C>A (p.P112Q) alteration is located in exon 4 (coding exon 3) of the PRRC2A gene. This alteration results from a C to A substitution at nucleotide position 335, causing the proline (P) at amino acid position 112 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.0065

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

PhyloP100

0.70

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.14

Sift

Benign

0.095

T;T

Sift4G

Uncertain

0.016

D;D

Polyphen

0.96

D;D

Vest4

0.26

MVP

0.093

MPC

0.89

ClinPred

0.039

GERP RS

3.0

PromoterAI

0.0052

Neutral

(source)

Varity_R

0.21

gMVP

0.32

Mutation Taster

=91/9

polymorphism

(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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6-31624305-C-A

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