6-31624287-C-T

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.317C>T(p.Pro106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,613,766 control chromosomes in the GnomAD database, including 3,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.048 ( 325 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3327 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.11

Publications

32 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015362501).

BP6

Variant 6-31624287-C-T is Benign according to our data. Variant chr6-31624287-C-T is described in ClinVar as [Benign]. Clinvar id is 3059974.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 4 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 4 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.317C>T	p.Pro106Leu	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.317C>T	p.Pro106Leu	missense_variant	Exon 4 of 31	1	NM_004638.4	ENSP00000365201.2	P48634-1
PRRC2A	ENST00000376007.8 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 4 of 31	1		ENSP00000365175.4	P48634-1
ENSG00000289282	ENST00000687518.1 link	c.63C>T	p.Ala21Ala	synonymous_variant	Exon 2 of 5			ENSP00000509222.1	A0A8I5QKQ9
PRRC2A	ENST00000469577.5 link	n.162C>T		non_coding_transcript_exon_variant	Exon 2 of 8	5

Frequencies

GnomAD3 genomes

AF:

0.0480

AC:

7310

AN:

152162

Hom.:

325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.0323

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0331

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0570

Gnomad OTH

AF:

0.0445

GnomAD2 exomes

AF:

0.0650

AC:

16162

AN:

248676

AF XY:

0.0687

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0237

Gnomad ASJ exome

AF:

0.0626

Gnomad EAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0539

GnomAD4 exome

AF:

0.0599

AC:

87602

AN:

1461486

Hom.:

3327

Cov.:

AF XY:

0.0615

AC XY:

44743

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.0107

AC:

358

AN:

33476

American (AMR)

AF:

0.0265

AC:

1186

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

1634

AN:

26136

East Asian (EAS)

AF:

0.143

AC:

5681

AN:

39700

South Asian (SAS)

AF:

0.117

AC:

10104

AN:

86250

European-Finnish (FIN)

AF:

0.0349

AC:

1855

AN:

53128

Middle Eastern (MID)

AF:

0.0406

AC:

234

AN:

5762

European-Non Finnish (NFE)

AF:

0.0564

AC:

62676

AN:

1111926

Other (OTH)

AF:

0.0642

AC:

3874

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

4823

9646

14470

19293

24116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0480

AC:

7308

AN:

152280

Hom.:

325

Cov.:

AF XY:

0.0494

AC XY:

3676

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0104

AC:

432

AN:

41582

American (AMR)

AF:

0.0324

AC:

495

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0599

AC:

208

AN:

3470

East Asian (EAS)

AF:

0.212

AC:

1097

AN:

5174

South Asian (SAS)

AF:

0.123

AC:

592

AN:

4824

European-Finnish (FIN)

AF:

0.0331

AC:

351

AN:

10602

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0570

AC:

3874

AN:

68016

Other (OTH)

AF:

0.0464

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

343

686

1029

1372

1715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0505

Hom.:

311

Bravo

AF:

0.0450

TwinsUK

AF:

0.0512

AC:

190

ALSPAC

AF:

0.0545

AC:

210

ESP6500AA

AF:

0.0142

AC:

ESP6500EA

AF:

0.0591

AC:

320

ExAC

AF:

0.0643

AC:

7797

Asia WGS

AF:

0.123

AC:

426

AN:

3478

EpiCase

AF:

0.0594

EpiControl

AF:

0.0594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Apr 08, 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

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.70

.;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

PhyloP100

2.1

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.0

D;D

REVEL

Benign

0.10

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.012

D;D

Polyphen

0.34

B;B

Vest4

0.20

MPC

0.98

ClinPred

0.059

GERP RS

3.9

PromoterAI

0.0034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.20

gMVP

0.46

Mutation Taster

=90/10

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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6-31624287-C-T

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