rs1046080

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004638.4(PRRC2A):c.1631C>A(p.Thr544Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,612,820 control chromosomes in the GnomAD database, including 455,099 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 (no stars).

Frequency

Genomes: 𝑓 0.74 ( 42349 hom., cov: 31)

Exomes 𝑓: 0.75 ( 412750 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.78

Publications

78 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=5.3481995E-7).

BP6

Variant 6-31628105-C-A is Benign according to our data. Variant chr6-31628105-C-A is described in ClinVar as Benign. ClinVar VariationId is 3060200.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.1631C>A	p.Thr544Lys	missense_variant	Exon 12 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.1631C>A	p.Thr544Lys	missense_variant	Exon 12 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.1631C>A	p.Thr544Lys	missense_variant	Exon 12 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.1631C>A	p.Thr544Lys	missense_variant	Exon 12 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1
PRRC2A	ENST00000376007.8 link	c.1631C>A	p.Thr544Lys	missense_variant	Exon 12 of 31	1		ENSP00000365175.4		P48634-1

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112899

AN:

151872

Hom.:

42320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.769

Gnomad ASJ

AF:

0.883

Gnomad EAS

AF:

0.973

Gnomad SAS

AF:

0.839

Gnomad FIN

AF:

0.816

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.755

GnomAD2 exomes

AF:

0.792

AC:

195889

AN:

247322

AF XY:

0.791

show subpopulations

Gnomad AFR exome

AF:

0.668

Gnomad AMR exome

AF:

0.849

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

0.980

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.746

Gnomad OTH exome

AF:

0.778

GnomAD4 exome

AF:

0.749

AC:

1093803

AN:

1460830

Hom.:

412750

Cov.:

AF XY:

0.751

AC XY:

545931

AN XY:

726722

show subpopulations

African (AFR)

AF:

0.667

AC:

22318

AN:

33476

American (AMR)

AF:

0.840

AC:

37572

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

23236

AN:

26136

East Asian (EAS)

AF:

0.982

AC:

39003

AN:

39700

South Asian (SAS)

AF:

0.810

AC:

69831

AN:

86256

European-Finnish (FIN)

AF:

0.796

AC:

41732

AN:

52404

Middle Eastern (MID)

AF:

0.809

AC:

4666

AN:

5768

European-Non Finnish (NFE)

AF:

0.728

AC:

809551

AN:

1111980

Other (OTH)

AF:

0.760

AC:

45894

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19053

38106

57158

76211

95264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20030

40060

60090

80120

100150

<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:

0.743

AC:

112972

AN:

151990

Hom.:

42349

Cov.:

AF XY:

0.750

AC XY:

55724

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.667

AC:

27646

AN:

41430

American (AMR)

AF:

0.769

AC:

11748

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.883

AC:

3067

AN:

3472

East Asian (EAS)

AF:

0.973

AC:

5024

AN:

5162

South Asian (SAS)

AF:

0.839

AC:

4039

AN:

4816

European-Finnish (FIN)

AF:

0.816

AC:

8623

AN:

10564

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.739

AC:

50205

AN:

67958

Other (OTH)

AF:

0.759

AC:

1602

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1469

2939

4408

5878

7347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<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:

0.754

Hom.:

185269

Bravo

AF:

0.737

TwinsUK

AF:

0.730

AC:

2705

ALSPAC

AF:

0.719

AC:

2772

ESP6500AA

AF:

0.684

AC:

2068

ESP6500EA

AF:

0.743

AC:

4024

ExAC

AF:

0.786

AC:

93014

Asia WGS

AF:

0.904

AC:

3141

AN:

3478

EpiCase

AF:

0.765

EpiControl

AF:

0.767

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Oct 17, 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

0.040

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.066

.;T

MetaRNN

Benign

5.3e-7

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.90

N;N

PhyloP100

1.8

PrimateAI

Uncertain

0.60

PROVEAN

Benign

2.3

N;N

REVEL

Benign

0.14

Sift

Benign

0.51

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.0

B;B

Vest4

0.043

MPC

0.19

ClinPred

0.013

GERP RS

4.6

Varity_R

0.028

gMVP

0.20

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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