Genetic Variant PRRC2A:p.Ser5Trp (chr6-31622803-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004638.4(PRRC2A):c.14C>G(p.Ser5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,462 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. S5L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

0 publications found

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]

PRRC2A links:

ENSG00000291302 (HGNC:):

ENSG00000291302 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.14C>G	p.Ser5Trp	missense_variant	Exon 2 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.14C>G	p.Ser5Trp	missense_variant	Exon 2 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.14C>G	p.Ser5Trp	missense_variant	Exon 2 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRRC2A	ENST00000376033.3 link	c.14C>G	p.Ser5Trp	missense_variant	Exon 2 of 31	1	NM_004638.4	ENSP00000365201.2	P48634-1
PRRC2A	ENST00000376007.8 link	c.14C>G	p.Ser5Trp	missense_variant	Exon 2 of 31	1		ENSP00000365175.4	P48634-1
ENSG00000291302	ENST00000706625.1 link	c.30C>G	p.Leu10Leu	synonymous_variant	Exon 1 of 1			ENSP00000516471.1	A0A9L9PY68
PRRC2A	ENST00000469577.5 link	n.136-1458C>G		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111912

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.070

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.97

.;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M

PhyloP100

1.8

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.041

D;D

Polyphen

1.0

D;D

Vest4

0.61

MutPred

0.43

Gain of MoRF binding (P = 0.0027);Gain of MoRF binding (P = 0.0027);

MVP

0.19

MPC

1.3

ClinPred

0.97

GERP RS

3.8

Varity_R

0.28

gMVP

0.71

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over