6-31625489-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004638.4(PRRC2A):c.637C>T(p.Arg213Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R213H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.637C>T	p.Arg213Cys	missense_variant	Exon 7 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.637C>T	p.Arg213Cys	missense_variant	Exon 7 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.637C>T	p.Arg213Cys	missense_variant	Exon 7 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.637C>T	p.Arg213Cys	missense_variant	Exon 7 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1
ENSG00000289282	ENST00000687518.1 link	c.383C>T	p.Ala128Val	missense_variant	Exon 5 of 5			ENSP00000509222.1		A0A8I5QKQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000424

AC:

AN:

235968

AF XY:

0.00000791

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000935

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1435930

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33004

American (AMR)

AF:

0.00

AC:

AN:

43468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24612

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1095368

Other (OTH)

AF:

0.00

AC:

AN:

59242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.637C>T (p.R213C) alteration is located in exon 7 (coding exon 6) of the PRRC2A gene. This alteration results from a C to T substitution at nucleotide position 637, causing the arginine (R) at amino acid position 213 to be replaced by a cysteine (C). 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

Benign

0.25

BayesDel_addAF

Benign

0.0071

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

.;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

1.8

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.99

D;D

Vest4

0.47

MutPred

0.31

Loss of methylation at R213 (P = 0.0099);Loss of methylation at R213 (P = 0.0099);

MVP

0.10

MPC

0.21

ClinPred

0.95

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.48

gMVP

0.50

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.21

Position offset: -6

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over