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GeneBe

6-31622898-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004638.4(PRRC2A):c.109G>A(p.Ala37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.018859953).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRRC2ANM_004638.4 linkuse as main transcriptc.109G>A p.Ala37Thr missense_variant 2/31 ENST00000376033.3
PRRC2ANM_080686.3 linkuse as main transcriptc.109G>A p.Ala37Thr missense_variant 2/31
PRRC2AXM_047419336.1 linkuse as main transcriptc.109G>A p.Ala37Thr missense_variant 2/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRRC2AENST00000376033.3 linkuse as main transcriptc.109G>A p.Ala37Thr missense_variant 2/311 NM_004638.4 P1P48634-1
PRRC2AENST00000376007.8 linkuse as main transcriptc.109G>A p.Ala37Thr missense_variant 2/311 P1P48634-1
PRRC2AENST00000469577.5 linkuse as main transcriptn.136-1363G>A intron_variant, non_coding_transcript_variant 5
ENST00000706625.1 linkuse as main transcript downstream_gene_variant P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000756
AC:
19
AN:
251398
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000199
AC:
29
AN:
1459788
Hom.:
0
Cov.:
29
AF XY:
0.0000138
AC XY:
10
AN XY:
726392
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.000425
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:
0.00000721
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152318
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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
Alfa
AF:
0.0000250
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 14, 2021The c.109G>A (p.A37T) alteration is located in exon 2 (coding exon 1) of the PRRC2A gene. This alteration results from a G to A substitution at nucleotide position 109, causing the alanine (A) at amino acid position 37 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.56
Cadd
Benign
21
Dann
Benign
0.89
DEOGEN2
Benign
0.0027
T;T
Eigen
Benign
-0.46
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.72
D
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.019
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.32
N;N
MutationTaster
Benign
0.87
D;D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.54
N;N
REVEL
Benign
0.051
Sift
Benign
0.62
T;T
Sift4G
Benign
0.56
T;T
Polyphen
0.019
B;B
Vest4
0.098
MutPred
0.52
Gain of glycosylation at A37 (P = 0.0205);Gain of glycosylation at A37 (P = 0.0205);
MVP
0.11
MPC
0.93
ClinPred
0.057
T
GERP RS
2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.065
gMVP
0.31

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: rs115229219; hg19: chr6-31590675; API