rs2280801

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004638.4(PRRC2A):​c.317C>A​(p.Pro106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P106L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRRC2ANM_004638.4 linkuse as main transcriptc.317C>A p.Pro106Gln missense_variant 4/31 ENST00000376033.3
PRRC2ANM_080686.3 linkuse as main transcriptc.317C>A p.Pro106Gln missense_variant 4/31
PRRC2AXM_047419336.1 linkuse as main transcriptc.317C>A p.Pro106Gln missense_variant 4/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRRC2AENST00000376033.3 linkuse as main transcriptc.317C>A p.Pro106Gln missense_variant 4/311 NM_004638.4 P1P48634-1
PRRC2AENST00000376007.8 linkuse as main transcriptc.317C>A p.Pro106Gln missense_variant 4/311 P1P48634-1
ENST00000687518.1 linkuse as main transcriptc.63C>A p.Ala21= synonymous_variant 2/5 P1
PRRC2AENST00000469577.5 linkuse as main transcriptn.162C>A non_coding_transcript_exon_variant 2/85

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248676
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134926
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461536
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727034
show subpopulations
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:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
22
DANN
Benign
0.94
DEOGEN2
Benign
0.029
T;T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.77
.;T
M_CAP
Benign
0.0097
T
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
8.5e-7
P;P
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.8
D;D
REVEL
Benign
0.10
Sift
Benign
0.12
T;T
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;D
Vest4
0.44
MutPred
0.29
Loss of glycosylation at P106 (P = 0.009);Loss of glycosylation at P106 (P = 0.009);
MVP
0.12
MPC
0.89
ClinPred
0.76
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.22
gMVP
0.45

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2280801; hg19: chr6-31592064; API