rs3130071

chr6-31626851-T-A

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.1062T>A(p.Gly354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,608,150 control chromosomes in the GnomAD database, including 627,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.91 (63830 hom., cov: 30)
  • Exomes 𝑓: 0.88 (563411 hom.)
• Consequence: PRRC2A NM_004638.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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=-0.57).
• BP6: Variant 6-31626851-T-A is Benign according to our data. Variant chr6-31626851-T-A is described in ClinVar as [Benign]. Clinvar id is 3060526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRC2A	NM_004638.4	c.1062T>A	p.Gly354=	synonymous_variant	10/31	ENST00000376033.3
PRRC2A	NM_080686.3	c.1062T>A	p.Gly354=	synonymous_variant	10/31
PRRC2A	XM_047419336.1	c.1062T>A	p.Gly354=	synonymous_variant	10/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3	c.1062T>A	p.Gly354=	synonymous_variant	10/31	1	NM_004638.4	P1
PRRC2A	ENST00000376007.8	c.1062T>A	p.Gly354=	synonymous_variant	10/31	1		P1
PRRC2A	ENST00000464890.1	n.489T>A		non_coding_transcript_exon_variant	2/3	2
PRRC2A	ENST00000469577.5	n.907T>A		non_coding_transcript_exon_variant	8/8	5

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139031 AN: 152076 Hom.: 63766 Cov.: 30

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.937

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.938

GnomAD3 exomes AF: 0.916 AC: 218713 AN: 238852 Hom.: 100549 AF XY: 0.916 AC XY: 118966 AN XY: 129872

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.957

Gnomad ASJ exome AF: 0.973

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.974

Gnomad FIN exome AF: 0.867

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.908

GnomAD4 exome AF: 0.878 AC: 1278678 AN: 1455956 Hom.: 563411 Cov.: 61 AF XY: 0.881 AC XY: 637953 AN XY: 723796

Gnomad4 AFR exome AF: 0.980

Gnomad4 AMR exome AF: 0.956

Gnomad4 ASJ exome AF: 0.971

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.972

Gnomad4 FIN exome AF: 0.865

Gnomad4 NFE exome AF: 0.858

Gnomad4 OTH exome AF: 0.893

GnomAD4 genome AF: 0.914 AC: 139153 AN: 152194 Hom.: 63830 Cov.: 30 AF XY: 0.916 AC XY: 68150 AN XY: 74404

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.938

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.877

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.939

Alfa AF: 0.883 Hom.: 44894

Bravo AF: 0.922

Asia WGS AF: 0.980 AC: 3409 AN: 3478

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 17, 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	-0.57
Cadd	Benign	8.3
Dann	Benign	0.85
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: rs3130071; hg19: chr6-31594628;