Genetic Variant PRRC2A:c.112+68C>T (chr6-31622969-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.112+68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,297,820 control chromosomes in the GnomAD database, including 1,045 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 0.023 ( 160 hom., cov: 32)

Exomes 𝑓: 0.025 ( 885 hom. )

Consequence

PRRC2A
NM_004638.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

2 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:

ENSG00000291302 (HGNC:):

ENSG00000291302 links:

SNORA38 (HGNC:32631): (small nucleolar RNA, H/ACA box 38)

SNORA38 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 = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.112+68C>T	intron_variant	Intron 2 of 30	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.112+68C>T	intron_variant	Intron 2 of 30		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.112+68C>T	intron_variant	Intron 2 of 29		XP_047275292.1
SNORA38	NR_002971.1 link	n.-110C>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.112+68C>T		intron_variant	Intron 2 of 30	1	NM_004638.4	ENSP00000365201.2		P48634-1
ENSG00000291302	ENST00000706625.1 link	c.*109C>T		downstream_gene_variant				ENSP00000516471.1		A0A9L9PY68

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3509

AN:

152124

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.0665

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.0247

AC:

28284

AN:

1145578

Hom.:

885

Cov.:

AF XY:

0.0264

AC XY:

15448

AN XY:

585314

show subpopulations

African (AFR)

AF:

0.00353

AC:

AN:

26904

American (AMR)

AF:

0.0148

AC:

635

AN:

42852

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

477

AN:

24126

East Asian (EAS)

AF:

0.135

AC:

5149

AN:

38214

South Asian (SAS)

AF:

0.0658

AC:

5231

AN:

79490

European-Finnish (FIN)

AF:

0.0231

AC:

1223

AN:

52988

Middle Eastern (MID)

AF:

0.0199

AC:

103

AN:

5172

European-Non Finnish (NFE)

AF:

0.0169

AC:

13946

AN:

825722

Other (OTH)

AF:

0.0284

AC:

1425

AN:

50110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1491

2982

4474

5965

7456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.0231

AC:

3511

AN:

152242

Hom.:

160

Cov.:

AF XY:

0.0249

AC XY:

1856

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00402

AC:

167

AN:

41544

American (AMR)

AF:

0.0190

AC:

290

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3470

East Asian (EAS)

AF:

0.198

AC:

1025

AN:

5170

South Asian (SAS)

AF:

0.0662

AC:

319

AN:

4820

European-Finnish (FIN)

AF:

0.0232

AC:

246

AN:

10606

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0197

AC:

1337

AN:

68024

Other (OTH)

AF:

0.0199

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

168

335

503

670

838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0220

Hom.:

170

Bravo

AF:

0.0209

Asia WGS

AF:

0.101

AC:

349

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

0.46

(source)

DANN

Benign

0.75

PhyloP100

-1.6

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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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