NM_004638.4:c.2254+131G>A

Variant names:

• chr6-31629976-G-A
• rs2242660
• NM_004638.4:c.2254+131G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004638.4(PRRC2A):​c.2254+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,422,916 control chromosomes in the GnomAD database, including 113,400 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (16268 hom., cov: 32)
  • Exomes 𝑓: 0.39 (97132 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 46 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.2254+131G>A		intron_variant	Intron 14 of 30	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.2254+131G>A		intron_variant	Intron 14 of 30		NP_542417.2
PRRC2A	XM_047419336.1	c.2254+131G>A		intron_variant	Intron 14 of 29		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.2254+131G>A		intron_variant	Intron 14 of 30	1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.2254+131G>A		intron_variant	Intron 14 of 30	1		ENSP00000365175.4
PRRC2A	ENST00000483470.1	n.*208G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68838 AN: 151860 Hom.: 16243 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.387 AC: 492137 AN: 1270938 Hom.: 97132 AF XY: 0.385 AC XY: 241558 AN XY: 627180

African (AFR) AF: 0.610 AC: 17104 AN: 28056

American (AMR) AF: 0.436 AC: 11961 AN: 27444

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 6671 AN: 19458

East Asian (EAS) AF: 0.420 AC: 15765 AN: 37546

South Asian (SAS) AF: 0.386 AC: 26156 AN: 67794

European-Finnish (FIN) AF: 0.482 AC: 20558 AN: 42612

Middle Eastern (MID) AF: 0.349 AC: 1435 AN: 4108

European-Non Finnish (NFE) AF: 0.375 AC: 371290 AN: 991008

Other (OTH) AF: 0.401 AC: 21197 AN: 52912

GnomAD4 genome AF: 0.453 AC: 68908 AN: 151978 Hom.: 16268 Cov.: 32 AF XY: 0.456 AC XY: 33884 AN XY: 74294

African (AFR) AF: 0.598 AC: 24793 AN: 41434

American (AMR) AF: 0.429 AC: 6559 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1167 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2057 AN: 5172

South Asian (SAS) AF: 0.403 AC: 1940 AN: 4816

European-Finnish (FIN) AF: 0.502 AC: 5298 AN: 10558

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25743 AN: 67946

Other (OTH) AF: 0.442 AC: 930 AN: 2106

Alfa AF: 0.412 Hom.: 36015

Bravo AF: 0.456

Asia WGS AF: 0.479 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.69
PhyloP100		0.36
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: rs2242660; hg19: chr6-31597753;