Genetic Variant PRRC2A:c.759+88A>G (chr6-31625699-A-G) – 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.759+88A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,582,172 control chromosomes in the GnomAD database, including 112,291 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 0.30 ( 8621 hom., cov: 31)

Exomes 𝑓: 0.37 ( 103670 hom. )

Consequence

PRRC2A
NM_004638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.826

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.759+88A>G	intron_variant	Intron 7 of 30	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.759+88A>G	intron_variant	Intron 7 of 30		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.759+88A>G	intron_variant	Intron 7 of 29		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.759+88A>G		intron_variant	Intron 7 of 30	1	NM_004638.4	ENSP00000365201.2		P48634-1
ENSG00000289282	ENST00000687518.1 link	c.*200A>G		downstream_gene_variant				ENSP00000509222.1		A0A8I5QKQ9

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45602

AN:

151958

Hom.:

8613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0798

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.371

AC:

530115

AN:

1430096

Hom.:

103670

Cov.:

AF XY:

0.379

AC XY:

270129

AN XY:

713132

show subpopulations

Gnomad4 AFR exome

AF:

0.0701

AC:

2295

AN:

32758

Gnomad4 AMR exome

AF:

0.409

AC:

18239

AN:

44584

Gnomad4 ASJ exome

AF:

0.547

AC:

14160

AN:

25888

Gnomad4 EAS exome

AF:

0.568

AC:

22449

AN:

39500

Gnomad4 SAS exome

AF:

0.521

AC:

44565

AN:

85512

Gnomad4 FIN exome

AF:

0.317

AC:

16928

AN:

53376

Gnomad4 NFE exome

AF:

0.357

AC:

386669

AN:

1083402

Gnomad4 Remaining exome

AF:

0.374

AC:

22208

AN:

59358

Heterozygous variant carriers

18587

37174

55761

74348

92935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

12090

24180

36270

48360

60450

<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:

0.300

AC:

45621

AN:

152076

Hom.:

8621

Cov.:

AF XY:

0.305

AC XY:

22679

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0798

AC:

0.0797793

AN:

0.0797793

Gnomad4 AMR

AF:

0.347

AC:

0.347346

AN:

0.347346

Gnomad4 ASJ

AF:

0.547

AC:

0.547344

AN:

0.547344

Gnomad4 EAS

AF:

0.590

AC:

0.589957

AN:

0.589957

Gnomad4 SAS

AF:

0.528

AC:

0.528435

AN:

0.528435

Gnomad4 FIN

AF:

0.315

AC:

0.315466

AN:

0.315466

Gnomad4 NFE

AF:

0.366

AC:

0.366066

AN:

0.366066

Gnomad4 OTH

AF:

0.335

AC:

0.334597

AN:

0.334597

Heterozygous variant carriers

1469

2938

4407

5876

7345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.347

Hom.:

28721

Bravo

AF:

0.289

Asia WGS

AF:

0.540

AC:

1877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.3

DANN

Benign

0.44

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over