Variant 6-31635993-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004638.4(PRRC2A):c.5568A>G(p.Gln1856=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,611,550 control chromosomes in the GnomAD database, including 26,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2376 hom., cov: 31)

Exomes 𝑓: 0.18 ( 24252 hom. )

Consequence

PRRC2A
NM_004638.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.240

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=-0.68).

BP6

Variant 6-31635993-A-G is Benign according to our data. Variant chr6-31635993-A-G is described in ClinVar as [Benign]. Clinvar id is 3060509.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PRRC2A	NM_004638.4 linkuse as main transcript	c.5568A>G	p.Gln1856=	synonymous_variant	25/31	ENST00000376033.3
PRRC2A	NM_080686.3 linkuse as main transcript	c.5568A>G	p.Gln1856=	synonymous_variant	25/31
PRRC2A	XM_047419336.1 linkuse as main transcript	c.5568A>G	p.Gln1856=	synonymous_variant	25/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3 linkuse as main transcript	c.5568A>G	p.Gln1856=	synonymous_variant	25/31	1	NM_004638.4	P1	P48634-1
PRRC2A	ENST00000376007.8 linkuse as main transcript	c.5568A>G	p.Gln1856=	synonymous_variant	25/31	1		P1	P48634-1
PRRC2A	ENST00000487089.1 linkuse as main transcript	n.634A>G		non_coding_transcript_exon_variant	1/2	2
PRRC2A	ENST00000487839.1 linkuse as main transcript	n.502A>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25658

AN:

151856

Hom.:

2376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.0986

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0788

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.145

AC:

36390

AN:

251022

Hom.:

2991

AF XY:

0.145

AC XY:

19657

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0764

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:

256703

AN:

1459576

Hom.:

24252

Cov.:

AF XY:

0.174

AC XY:

126020

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0802

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:

0.191

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.169

AC:

25658

AN:

151974

Hom.:

2376

Cov.:

AF XY:

0.164

AC XY:

12202

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.0983

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.0794

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.148

Alfa

AF:

0.168

Hom.:

3260

Bravo

AF:

0.166

Asia WGS

AF:

0.0950

AC:

331

AN:

3478

EpiCase

AF:

0.173

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.68

CADD

Benign

6.0

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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