6-31628105-C-G

Position:

• chr6-31628105-C-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.1631C>G​(p.Thr544Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T544K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRRC2A NM_004638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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=0.04131326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRRC2A	NM_004638.4	c.1631C>G	p.Thr544Arg	missense_variant	12/31	ENST00000376033.3	NP_004629.3
PRRC2A	NM_080686.3	c.1631C>G	p.Thr544Arg	missense_variant	12/31		NP_542417.2
PRRC2A	XM_047419336.1	c.1631C>G	p.Thr544Arg	missense_variant	12/30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3	c.1631C>G	p.Thr544Arg	missense_variant	12/31	1	NM_004638.4	ENSP00000365201.2
PRRC2A	ENST00000376007.8	c.1631C>G	p.Thr544Arg	missense_variant	12/31	1		ENSP00000365175.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460878 Hom.: 0 Cov.: 93 AF XY: 0.00 AC XY: 0 AN XY: 726742

Gnomad4 AFR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.0027	T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.13	.;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	1.5	N;N
REVEL	Benign	0.11
Sift	Benign	0.14	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0	B;B
Vest4		0.077
MutPred		0.27		Loss of phosphorylation at T544 (P = 0.0075);Loss of phosphorylation at T544 (P = 0.0075);
MVP		0.043
MPC		0.18
ClinPred		0.46	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.040
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1046080; hg19: chr6-31595882;