rs11229

chr6-31635993-A-Cchr6-31635993-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004638.4(PRRC2A):c.5568A>C(p.Gln1856His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q1856Q) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046233386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRRC2A	NM_004638.4	c.5568A>C	p.Gln1856His	missense_variant	25/31	ENST00000376033.3
PRRC2A	NM_080686.3	c.5568A>C	p.Gln1856His	missense_variant	25/31
PRRC2A	XM_047419336.1	c.5568A>C	p.Gln1856His	missense_variant	25/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3	c.5568A>C	p.Gln1856His	missense_variant	25/31	1	NM_004638.4	P1
PRRC2A	ENST00000376007.8	c.5568A>C	p.Gln1856His	missense_variant	25/31	1		P1
PRRC2A	ENST00000487089.1	n.634A>C		non_coding_transcript_exon_variant	1/2	2
PRRC2A	ENST00000487839.1	n.502A>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151914 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460778 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726762

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151914 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74160

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	15
Dann	Benign	0.71
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.63	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	0.90	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.24	N;N
REVEL	Benign	0.089
Sift	Benign	0.20	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0010	B;B
Vest4		0.23
MutPred		0.15		Gain of glycosylation at S1855 (P = 0.1684);Gain of glycosylation at S1855 (P = 0.1684);
MVP		0.068
MPC		0.15
ClinPred		0.081	T
GERP RS		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.38

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: rs11229; hg19: chr6-31603770;