Variant 6-31625805-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004638.4(PRRC2A):c.773A>G(p.Tyr258Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,580,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

PRRC2A
NM_004638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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:

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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
PRRC2A	NM_004638.4 linkuse as main transcript	c.773A>G	p.Tyr258Cys	missense_variant	8/31	ENST00000376033.3
PRRC2A	NM_080686.3 linkuse as main transcript	c.773A>G	p.Tyr258Cys	missense_variant	8/31
PRRC2A	XM_047419336.1 linkuse as main transcript	c.773A>G	p.Tyr258Cys	missense_variant	8/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3 linkuse as main transcript	c.773A>G	p.Tyr258Cys	missense_variant	8/31	1	NM_004638.4	P1	P48634-1
PRRC2A	ENST00000376007.8 linkuse as main transcript	c.773A>G	p.Tyr258Cys	missense_variant	8/31	1		P1	P48634-1
PRRC2A	ENST00000464890.1 linkuse as main transcript	n.52A>G		non_coding_transcript_exon_variant	1/3	2
PRRC2A	ENST00000469577.5 linkuse as main transcript	n.618A>G		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000490

AC:

AN:

1428452

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712372

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000554

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.773A>G (p.Y258C) alteration is located in exon 8 (coding exon 7) of the PRRC2A gene. This alteration results from a A to G substitution at nucleotide position 773, causing the tyrosine (Y) at amino acid position 258 to be replaced by a cysteine (C). 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

Pathogenic

0.89

BayesDel_addAF

Benign

0.0068

BayesDel_noAF

Benign

-0.23

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.12

T;T

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

1.0

D;D

Vest4

0.69

MutPred

0.18

Loss of phosphorylation at Y258 (P = 0.0109);Loss of phosphorylation at Y258 (P = 0.0109);

MVP

0.18

MPC

0.20

ClinPred

0.96

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over