rs2260000

Positions:

• chr6-31625699-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.759+88A>G		intron_variant		ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.759+88A>G		intron_variant			NP_542417.2
PRRC2A	XM_047419336.1	c.759+88A>G		intron_variant			XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.759+88A>G		intron_variant		1	NM_004638.4	ENSP00000365201	P1
PRRC2A	ENST00000376007.8	c.759+88A>G		intron_variant		1		ENSP00000365175	P1
PRRC2A	ENST00000469577.5	n.604+88A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45602 AN: 151958 Hom.: 8613 Cov.: 31

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.: 32 AF XY: 0.379 AC XY: 270129 AN XY: 713132

Gnomad4 AFR exome AF: 0.0701

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.300 AC: 45621 AN: 152076 Hom.: 8621 Cov.: 31 AF XY: 0.305 AC XY: 22679 AN XY: 74334

Gnomad4 AFR AF: 0.0798

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.335

Alfa AF: 0.371 Hom.: 10131

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

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: rs2260000; hg19: chr6-31593476;