rs2280801

Variant names:

• chr6-31624287-C-T
• rs2280801
• NM_004638.4:c.317C>T
• PRRC2A p.Pro106Leu

Your query was ambiguous. Multiple possible variants found:

• chr6-31624287-C-T
• chr6-31624287-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.048 (325 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3327 hom.)
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.11
• Publications: 32 publications found

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]

ENSG00000289282 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 3059974.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	NM_004638.4	MANE Select	c.317C>T	p.Pro106Leu	missense	Exon 4 of 31	NP_004629.3
	PRRC2A	NM_080686.3		c.317C>T	p.Pro106Leu	missense	Exon 4 of 31	NP_542417.2	A0A1U9X974

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.317C>T	p.Pro106Leu	missense	Exon 4 of 31	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.317C>T	p.Pro106Leu	missense	Exon 4 of 31	ENSP00000365175.4	P48634-1
	ENSG00000289282	ENST00000687518.1		c.63C>T	p.Ala21Ala	synonymous	Exon 2 of 5	ENSP00000509222.1	A0A8I5QKQ9

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

GnomAD2 exomes AF: 0.0650 AC: 16162 AN: 248676 AF XY: 0.0687

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 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

African (AFR) AF: 0.0107 AC: 358 AN: 33476

American (AMR) AF: 0.0265 AC: 1186 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 1634 AN: 26136

East Asian (EAS) AF: 0.143 AC: 5681 AN: 39700

South Asian (SAS) AF: 0.117 AC: 10104 AN: 86250

European-Finnish (FIN) AF: 0.0349 AC: 1855 AN: 53128

Middle Eastern (MID) AF: 0.0406 AC: 234 AN: 5762

European-Non Finnish (NFE) AF: 0.0564 AC: 62676 AN: 1111926

Other (OTH) AF: 0.0642 AC: 3874 AN: 60384

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

African (AFR) AF: 0.0104 AC: 432 AN: 41582

American (AMR) AF: 0.0324 AC: 495 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1097 AN: 5174

South Asian (SAS) AF: 0.123 AC: 592 AN: 4824

European-Finnish (FIN) AF: 0.0331 AC: 351 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0570 AC: 3874 AN: 68016

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0505 Hom.: 311

Bravo AF: 0.0450

Asia WGS AF: 0.123 AC: 426 AN: 3478

EpiCase AF: 0.0594

EpiControl AF: 0.0594

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PRRC2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.035
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.10
Sift	Benign	0.061	T
Sift4G	Uncertain	0.012	D
PromoterAI		0.0034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.20
gMVP		0.46
Mutation Taster		=90/10	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2280801;

hg19: chr6-31592064;