Variant rs3130626 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000376033.3(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 (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2375 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24306 hom. )

Consequence

PRRC2A
ENST00000376033.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0710

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 no_assertion_criteria_provided, 0 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	Protein
PRRC2A	NM_004638.4 linkuse as main transcript	c.2376A>G	p.Val792=	synonymous_variant	15/31	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3 linkuse as main transcript	c.2376A>G	p.Val792=	synonymous_variant	15/31		NP_542417.2
PRRC2A	XM_047419336.1 linkuse as main transcript	c.2376A>G	p.Val792=	synonymous_variant	15/30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 linkuse as main transcript	c.2376A>G	p.Val792=	synonymous_variant	15/31	1	NM_004638.4	ENSP00000365201	P1	P48634-1
PRRC2A	ENST00000376007.8 linkuse as main transcript	c.2376A>G	p.Val792=	synonymous_variant	15/31	1		ENSP00000365175	P1	P48634-1

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25655

AN:

151062

Hom.:

2375

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.174

AC XY:

126406

AN XY:

726850

show subpopulations

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.:

AF XY:

0.165

AC XY:

12207

AN XY:

73916

show subpopulations

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: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Benign, no assertion criteria provided

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over