6-31624287-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004638.4(PRRC2A):c.317C>T(p.Pro106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 1,613,766 control chromosomes in the GnomAD database, including 3,652 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.048 (325 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3327 hom.)
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015362501).
• BP6: Variant 6-31624287-C-T is Benign according to our data. Variant chr6-31624287-C-T is described in ClinVar as [Benign]. Clinvar id is 3059974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRC2A	NM_004638.4	c.317C>T	p.Pro106Leu	missense_variant	4/31	ENST00000376033.3
PRRC2A	NM_080686.3	c.317C>T	p.Pro106Leu	missense_variant	4/31
PRRC2A	XM_047419336.1	c.317C>T	p.Pro106Leu	missense_variant	4/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3	c.317C>T	p.Pro106Leu	missense_variant	4/31	1	NM_004638.4	P1
PRRC2A	ENST00000376007.8	c.317C>T	p.Pro106Leu	missense_variant	4/31	1		P1
	ENST00000687518.1	c.63C>T	p.Ala21=	synonymous_variant	2/5			P1
PRRC2A	ENST00000469577.5	n.162C>T		non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7310 AN: 152162 Hom.: 325 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0331

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0445

GnomAD3 exomes AF: 0.0650 AC: 16162 AN: 248676 Hom.: 887 AF XY: 0.0687 AC XY: 9268 AN XY: 134926

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0626

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.0543

Gnomad OTH exome AF: 0.0539

GnomAD4 exome AF: 0.0599 AC: 87602 AN: 1461486 Hom.: 3327 Cov.: 34 AF XY: 0.0615 AC XY: 44743 AN XY: 727020

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.0625

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.0642

GnomAD4 genome AF: 0.0480 AC: 7308 AN: 152280 Hom.: 325 Cov.: 32 AF XY: 0.0494 AC XY: 3676 AN XY: 74444

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0331

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0515 Hom.: 204

Bravo AF: 0.0450

TwinsUK AF: 0.0512 AC: 190

ALSPAC AF: 0.0545 AC: 210

ESP6500AA AF: 0.0142 AC: 43

ESP6500EA AF: 0.0591 AC: 320

ExAC AF: 0.0643 AC: 7797

Asia WGS AF: 0.123 AC: 426 AN: 3478

EpiCase AF: 0.0594

EpiControl AF: 0.0594

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

Apr 08, 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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	0.98
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	0.035
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.8e-9	P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Benign	0.10
Sift	Benign	0.061	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.34	B;B
Vest4		0.20
MPC		0.98
ClinPred		0.059	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.20
gMVP		0.46

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: rs2280801; hg19: chr6-31592064;