rs3130626

Variant names:

• chr6-31630712-A-G
• rs3130626
• NM_004638.4:c.2376A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_004638.4(PRRC2A):​c.2376A>G​(p.Val792Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,116 control chromosomes in the GnomAD database, including 26,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2375 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24306 hom.)
• Consequence: PRRC2A NM_004638.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0710
• Publications: 47 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 (BayesDel_noAF=-0.5).
• BP6: Variant 6-31630712-A-G is Benign according to our data. Variant chr6-31630712-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059728.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.2376A>G	p.Val792Val	synonymous_variant	Exon 15 of 31	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.2376A>G	p.Val792Val	synonymous_variant	Exon 15 of 31		NP_542417.2
PRRC2A	XM_047419336.1	c.2376A>G	p.Val792Val	synonymous_variant	Exon 15 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.2376A>G	p.Val792Val	synonymous_variant	Exon 15 of 31	1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.2376A>G	p.Val792Val	synonymous_variant	Exon 15 of 31	1		ENSP00000365175.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25655 AN: 151062 Hom.: 2375 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0991

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.145 AC: 36450 AN: 251268 AF XY: 0.145

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0766

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.0961

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.176 AC: 257607 AN: 1460932 Hom.: 24306 Cov.: 35 AF XY: 0.174 AC XY: 126406 AN XY: 726850

African (AFR) AF: 0.211 AC: 6907 AN: 32740

American (AMR) AF: 0.0805 AC: 3596 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3111 AN: 26136

East Asian (EAS) AF: 0.0466 AC: 1851 AN: 39700

South Asian (SAS) AF: 0.115 AC: 9911 AN: 86252

European-Finnish (FIN) AF: 0.160 AC: 8535 AN: 53418

Middle Eastern (MID) AF: 0.0921 AC: 531 AN: 5766

European-Non Finnish (NFE) AF: 0.192 AC: 213191 AN: 1111968

Other (OTH) AF: 0.165 AC: 9974 AN: 60296

GnomAD4 genome AF: 0.170 AC: 25655 AN: 151184 Hom.: 2375 Cov.: 32 AF XY: 0.165 AC XY: 12207 AN XY: 73916

African (AFR) AF: 0.197 AC: 8012 AN: 40604

American (AMR) AF: 0.0988 AC: 1507 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3466

East Asian (EAS) AF: 0.0783 AC: 406 AN: 5182

South Asian (SAS) AF: 0.124 AC: 597 AN: 4820

European-Finnish (FIN) AF: 0.160 AC: 1698 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12515 AN: 67970

Other (OTH) AF: 0.148 AC: 313 AN: 2108

Alfa AF: 0.184 Hom.: 8662

Bravo AF: 0.166

EpiCase AF: 0.173

EpiControl AF: 0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PRRC2A-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	-0.50
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		0.071
Mutation Taster		=99/1	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: rs3130626; hg19: chr6-31598489; COSMIC: COSV65687512; COSMIC: COSV65687512;