Genetic Variant PRRC2A:c.2254+78C>T (chr6-31629923-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004638.4(PRRC2A):c.2254+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,571,048 control chromosomes in the GnomAD database, including 28,153 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2602 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25551 hom. )

Consequence

PRRC2A
NM_004638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

37 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.2254+78C>T	intron_variant	Intron 14 of 30	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.2254+78C>T	intron_variant	Intron 14 of 30		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.2254+78C>T	intron_variant	Intron 14 of 29		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRRC2A	ENST00000376033.3 link	c.2254+78C>T	intron_variant	Intron 14 of 30	1	NM_004638.4	ENSP00000365201.2	P48634-1
PRRC2A	ENST00000376007.8 link	c.2254+78C>T	intron_variant	Intron 14 of 30	1		ENSP00000365175.4	P48634-1
PRRC2A	ENST00000483470.1 link	n.*155C>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26965

AN:

152026

Hom.:

2602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.0786

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.183

AC:

260273

AN:

1418904

Hom.:

25551

AF XY:

0.181

AC XY:

127429

AN XY:

703356

show subpopulations

African (AFR)

AF:

0.216

AC:

6916

AN:

32016

American (AMR)

AF:

0.0836

AC:

3179

AN:

38046

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

2908

AN:

23248

East Asian (EAS)

AF:

0.0468

AC:

1834

AN:

39198

South Asian (SAS)

AF:

0.120

AC:

9636

AN:

80602

European-Finnish (FIN)

AF:

0.169

AC:

8691

AN:

51430

Middle Eastern (MID)

AF:

0.0956

AC:

523

AN:

5470

European-Non Finnish (NFE)

AF:

0.198

AC:

216437

AN:

1090440

Other (OTH)

AF:

0.174

AC:

10149

AN:

58454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

9309

18618

27926

37235

46544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.177

AC:

26972

AN:

152144

Hom.:

2602

Cov.:

AF XY:

0.173

AC XY:

12854

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.206

AC:

8562

AN:

41504

American (AMR)

AF:

0.106

AC:

1616

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

418

AN:

3470

East Asian (EAS)

AF:

0.0792

AC:

410

AN:

5176

South Asian (SAS)

AF:

0.128

AC:

618

AN:

4828

European-Finnish (FIN)

AF:

0.170

AC:

1797

AN:

10558

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.191

AC:

13015

AN:

67988

Other (OTH)

AF:

0.155

AC:

327

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1132

2264

3395

4527

5659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.190

Hom.:

8016

Bravo

AF:

0.175

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.36

PhyloP100

-1.1

Mutation Taster

=100/0

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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6-31629923-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over