rs2736158

Variant names:

• chr6-31632527-G-C
• rs2736158
• NM_004638.4:c.3854G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31632527-G-C
• chr6-31632527-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004638.4(PRRC2A):​c.3854G>C​(p.Gly1285Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 1,609,644 control chromosomes in the GnomAD database, including 2,178 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.066 (509 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1669 hom.)
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.64
• Publications: 21 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016219318).
• BP6: Variant 6-31632527-G-C is Benign according to our data. Variant chr6-31632527-G-C is described in ClinVar as Benign. ClinVar VariationId is 1229769.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 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.3854G>C	p.Gly1285Ala	missense	Exon 16 of 31	NP_004629.3
	PRRC2A	NM_080686.3		c.3854G>C	p.Gly1285Ala	missense	Exon 16 of 31	NP_542417.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.3854G>C	p.Gly1285Ala	missense	Exon 16 of 31	ENSP00000365201.2
	PRRC2A	ENST00000376007.8	TSL:1	c.3854G>C	p.Gly1285Ala	missense	Exon 16 of 31	ENSP00000365175.4

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10070 AN: 152066 Hom.: 509 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.00585

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0724

GnomAD2 exomes AF: 0.0489 AC: 11941 AN: 244426 AF XY: 0.0473

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.0488

Gnomad EAS exome AF: 0.142

Gnomad FIN exome AF: 0.00464

Gnomad NFE exome AF: 0.0271

Gnomad OTH exome AF: 0.0473

GnomAD4 exome AF: 0.0373 AC: 54378 AN: 1457460 Hom.: 1669 Cov.: 33 AF XY: 0.0374 AC XY: 27084 AN XY: 724604

African (AFR) AF: 0.146 AC: 4882 AN: 33420

American (AMR) AF: 0.0541 AC: 2411 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 1327 AN: 25930

East Asian (EAS) AF: 0.0977 AC: 3874 AN: 39640

South Asian (SAS) AF: 0.0541 AC: 4651 AN: 86022

European-Finnish (FIN) AF: 0.00608 AC: 317 AN: 52130

Middle Eastern (MID) AF: 0.130 AC: 749 AN: 5750

European-Non Finnish (NFE) AF: 0.0298 AC: 33092 AN: 1109806

Other (OTH) AF: 0.0511 AC: 3075 AN: 60208

GnomAD4 genome AF: 0.0662 AC: 10074 AN: 152184 Hom.: 509 Cov.: 32 AF XY: 0.0663 AC XY: 4928 AN XY: 74384

African (AFR) AF: 0.139 AC: 5778 AN: 41520

American (AMR) AF: 0.0613 AC: 937 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 173 AN: 3472

East Asian (EAS) AF: 0.131 AC: 677 AN: 5174

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4824

European-Finnish (FIN) AF: 0.00585 AC: 62 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0288 AC: 1961 AN: 67998

Other (OTH) AF: 0.0721 AC: 152 AN: 2108

Alfa AF: 0.0363 Hom.: 153

Bravo AF: 0.0736

TwinsUK AF: 0.0291 AC: 108

ALSPAC AF: 0.0293 AC: 113

ESP6500AA AF: 0.133 AC: 401

ESP6500EA AF: 0.0297 AC: 161

ExAC AF: 0.0482 AC: 5710

Asia WGS AF: 0.0790 AC: 274 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0319

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PRRC2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.061
Sift	Benign	0.14	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.21
MPC		0.17
ClinPred		0.013	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.11
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs2736158; hg19: chr6-31600304; COSMIC: COSV65686676; COSMIC: COSV65686676;