rs3130626

chr6-31630712-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004638.4(PRRC2A):c.2376A>G(p.Val792=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,116 control chromosomes in the GnomAD database, including 26,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2375 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24306 hom.)
• Consequence: PRRC2A NM_004638.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-31630712-A-G is Benign according to our data. Variant chr6-31630712-A-G is described in ClinVar as [Benign]. Clinvar id is 3059728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRC2A	NM_004638.4	c.2376A>G	p.Val792=	synonymous_variant	15/31	ENST00000376033.3
PRRC2A	NM_080686.3	c.2376A>G	p.Val792=	synonymous_variant	15/31
PRRC2A	XM_047419336.1	c.2376A>G	p.Val792=	synonymous_variant	15/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3	c.2376A>G	p.Val792=	synonymous_variant	15/31	1	NM_004638.4	P1
PRRC2A	ENST00000376007.8	c.2376A>G	p.Val792=	synonymous_variant	15/31	1		P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25655 AN: 151062 Hom.: 2375 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.145 AC: 36450 AN: 251268 Hom.: 2989 AF XY: 0.145 AC XY: 19696 AN XY: 135816

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0766

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0961

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.176 AC: 257607 AN: 1460932 Hom.: 24306 Cov.: 35 AF XY: 0.174 AC XY: 126406 AN XY: 726850

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.0805

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0466

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.170 AC: 25655 AN: 151184 Hom.: 2375 Cov.: 32 AF XY: 0.165 AC XY: 12207 AN XY: 73916

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0988

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.148

Alfa AF: 0.183 Hom.: 3322

Bravo AF: 0.166

EpiCase AF: 0.173

EpiControl AF: 0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PRRC2A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	7.1
Dann	Benign	0.68

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: rs3130626; hg19: chr6-31598489; COSMIC: COSV65687512; COSMIC: COSV65687512;