chr6-31636814-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.6016C>T(p.Pro2006Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,610,838 control chromosomes in the GnomAD database, including 26,622 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2006L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.17 ( 2380 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24242 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.57

Publications

56 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=0.0016311109).

BP6

Variant 6-31636814-C-T is Benign according to our data. Variant chr6-31636814-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058971.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.6016C>T	p.Pro2006Ser	missense_variant	Exon 28 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.6016C>T	p.Pro2006Ser	missense_variant	Exon 28 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.5934+206C>T		intron_variant	Intron 27 of 29		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.6016C>T	p.Pro2006Ser	missense_variant	Exon 28 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25650

AN:

152060

Hom.:

2380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0988

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0785

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.150

GnomAD2 exomes

AF:

0.145

AC:

35394

AN:

244646

AF XY:

0.145

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.0767

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0960

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.176

AC:

256955

AN:

1458660

Hom.:

24242

Cov.:

AF XY:

0.174

AC XY:

126120

AN XY:

725806

show subpopulations

African (AFR)

AF:

0.206

AC:

6903

AN:

33480

American (AMR)

AF:

0.0803

AC:

3592

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

3112

AN:

26136

East Asian (EAS)

AF:

0.0467

AC:

1853

AN:

39700

South Asian (SAS)

AF:

0.115

AC:

9904

AN:

86258

European-Finnish (FIN)

AF:

0.161

AC:

8068

AN:

50246

Middle Eastern (MID)

AF:

0.0915

AC:

528

AN:

5768

European-Non Finnish (NFE)

AF:

0.192

AC:

213030

AN:

1111972

Other (OTH)

AF:

0.165

AC:

9965

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

13646

27292

40938

54584

68230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7426

14852

22278

29704

37130

<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:

0.169

AC:

25650

AN:

152178

Hom.:

2380

Cov.:

AF XY:

0.164

AC XY:

12212

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.193

AC:

8000

AN:

41508

American (AMR)

AF:

0.0985

AC:

1506

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3470

East Asian (EAS)

AF:

0.0791

AC:

410

AN:

5184

South Asian (SAS)

AF:

0.124

AC:

599

AN:

4826

European-Finnish (FIN)

AF:

0.161

AC:

1709

AN:

10594

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12504

AN:

67986

Other (OTH)

AF:

0.149

AC:

314

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1091

2181

3272

4362

5453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.182

Hom.:

5030

Bravo

AF:

0.166

TwinsUK

AF:

0.190

AC:

706

ALSPAC

AF:

0.193

AC:

744

ESP6500AA

AF:

0.196

AC:

590

ESP6500EA

AF:

0.176

AC:

955

ExAC

AF:

0.148

AC:

17367

Asia WGS

AF:

0.0950

AC:

331

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Oct 21, 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

0.16

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.094

T;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.69

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.0

N;N

PhyloP100

3.6

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.97

D;D

Vest4

0.17

MPC

0.16

ClinPred

0.034

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.53

Mutation Taster

=100/0

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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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