NM_004638.4:c.5683T>G

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.5683T>G(p.Leu1895Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 1,612,854 control chromosomes in the GnomAD database, including 707,474 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 0.96 ( 69636 hom., cov: 30)

Exomes 𝑓: 0.93 ( 637838 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.63

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=5.334385E-7).

BP6

Variant 6-31636267-T-G is Benign according to our data. Variant chr6-31636267-T-G is described in ClinVar as Benign. ClinVar VariationId is 3059796.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	NM_004638.4	MANE Select	c.5683T>G	p.Leu1895Val	missense	Exon 26 of 31	NP_004629.3
	PRRC2A	NM_080686.3		c.5683T>G	p.Leu1895Val	missense	Exon 26 of 31	NP_542417.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.5683T>G	p.Leu1895Val	missense	Exon 26 of 31	ENSP00000365201.2
PRRC2A	ENST00000376007.8	TSL:1	c.5683T>G	p.Leu1895Val	missense	Exon 26 of 31	ENSP00000365175.4
PRRC2A	ENST00000487839.1	TSL:5	n.617T>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

AF:

0.956

AC:

145393

AN:

152064

Hom.:

69573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.986

Gnomad AMI

AF:

0.933

Gnomad AMR

AF:

0.973

Gnomad ASJ

AF:

0.991

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

0.925

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.930

Gnomad OTH

AF:

0.976

GnomAD2 exomes

AF:

0.958

AC:

235732

AN:

246132

AF XY:

0.959

show subpopulations

Gnomad AFR exome

AF:

0.988

Gnomad AMR exome

AF:

0.981

Gnomad ASJ exome

AF:

0.993

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.920

Gnomad NFE exome

AF:

0.932

Gnomad OTH exome

AF:

0.957

GnomAD4 exome

AF:

0.934

AC:

1364164

AN:

1460672

Hom.:

637838

Cov.:

AF XY:

0.936

AC XY:

680447

AN XY:

726660

show subpopulations

African (AFR)

AF:

0.989

AC:

33098

AN:

33480

American (AMR)

AF:

0.980

AC:

43836

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.992

AC:

25928

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39700

South Asian (SAS)

AF:

0.999

AC:

86212

AN:

86258

European-Finnish (FIN)

AF:

0.921

AC:

48193

AN:

52312

Middle Eastern (MID)

AF:

0.998

AC:

5759

AN:

5768

European-Non Finnish (NFE)

AF:

0.921

AC:

1024410

AN:

1111912

Other (OTH)

AF:

0.944

AC:

57030

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

5699

11397

17096

22794

28493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21524

43048

64572

86096

107620

<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:

0.956

AC:

145515

AN:

152182

Hom.:

69636

Cov.:

AF XY:

0.957

AC XY:

71174

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.986

AC:

40921

AN:

41490

American (AMR)

AF:

0.973

AC:

14875

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.991

AC:

3442

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5183

AN:

5184

South Asian (SAS)

AF:

1.00

AC:

4803

AN:

4804

European-Finnish (FIN)

AF:

0.925

AC:

9817

AN:

10610

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.930

AC:

63270

AN:

68018

Other (OTH)

AF:

0.976

AC:

2061

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

323

646

968

1291

1614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.942

Hom.:

307237

Bravo

AF:

0.960

TwinsUK

AF:

0.921

AC:

3416

ALSPAC

AF:

0.921

AC:

3551

ESP6500AA

AF:

0.984

AC:

2973

ESP6500EA

AF:

0.933

AC:

5055

ExAC

AF:

0.958

AC:

113094

Asia WGS

AF:

0.997

AC:

3467

AN:

3478

EpiCase

AF:

0.943

EpiControl

AF:

0.944

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.071

MetaRNN

Benign

5.3e-7

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-1.1

PhyloP100

1.6

PrimateAI

Uncertain

0.56

PROVEAN

Benign

1.2

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

0.91

Polyphen

0.0

Vest4

0.033

MPC

0.16

ClinPred

0.0063

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.25

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over