rs2736157

Positions:

• chr6-31633043-A-G
• chr6-31633043-A-T

Variant summary

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

The NM_004638.4(PRRC2A):​c.4319+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,450,738 control chromosomes in the GnomAD database, including 24,793 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 0.17 (2379 hom., cov: 32)
  • Exomes 𝑓: 0.18 (22414 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.4319+51A>G		intron_variant		ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.4319+51A>G		intron_variant			NP_542417.2
PRRC2A	XM_047419336.1	c.4319+51A>G		intron_variant			XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.4319+51A>G		intron_variant		1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.4319+51A>G		intron_variant		1		ENSP00000365175.4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25664 AN: 151982 Hom.: 2379 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0788

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.146 AC: 11244 AN: 76768 Hom.: 934 AF XY: 0.149 AC XY: 5898 AN XY: 39502

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0857

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.0965

Gnomad SAS exome AF: 0.115

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.180 AC: 234154 AN: 1298638 Hom.: 22414 Cov.: 32 AF XY: 0.178 AC XY: 112494 AN XY: 631260

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0879

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0409

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.169 AC: 25664 AN: 152100 Hom.: 2379 Cov.: 32 AF XY: 0.164 AC XY: 12218 AN XY: 74360

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.148

Alfa AF: 0.178 Hom.: 1670

Bravo AF: 0.166

Asia WGS AF: 0.0950 AC: 331 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	0.27
DANN	Benign	0.32
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1

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: rs2736157; hg19: chr6-31600820;