rs2242660

Positions:

• chr6-31629976-G-A
• chr6-31629976-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004638.4(PRRC2A):​c.2254+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,422,916 control chromosomes in the GnomAD database, including 113,400 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 0.45 (16268 hom., cov: 32)
  • Exomes 𝑓: 0.39 (97132 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.2254+131G>A		intron_variant		ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.2254+131G>A		intron_variant			NP_542417.2
PRRC2A	XM_047419336.1	c.2254+131G>A		intron_variant			XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.2254+131G>A		intron_variant		1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.2254+131G>A		intron_variant		1		ENSP00000365175.4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68838 AN: 151860 Hom.: 16243 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.387 AC: 492137 AN: 1270938 Hom.: 97132 AF XY: 0.385 AC XY: 241558 AN XY: 627180

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.453 AC: 68908 AN: 151978 Hom.: 16268 Cov.: 32 AF XY: 0.456 AC XY: 33884 AN XY: 74294

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.336

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.442

Alfa AF: 0.392 Hom.: 10929

Bravo AF: 0.456

Asia WGS AF: 0.479 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs2242660; hg19: chr6-31597753;