dbSNP rs569008444: PRRC2A:p.Asn203Ser (chr6-31625460-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004638.4(PRRC2A):c.608A>G(p.Asn203Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000138 in 1,447,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. N203I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PRRC2A
NM_004638.4 missense, splice_region

Scores

Splicing: ADA: 0.0004591

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.74

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:

ENSG00000289282 (HGNC:):

ENSG00000289282 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19277593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.608A>G	p.Asn203Ser	missense_variant, splice_region_variant	Exon 7 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.608A>G	p.Asn203Ser	missense_variant, splice_region_variant	Exon 7 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.608A>G	p.Asn203Ser	missense_variant, splice_region_variant	Exon 7 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2A	ENST00000376033.3 link	c.608A>G	p.Asn203Ser	missense_variant, splice_region_variant	Exon 7 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1
ENSG00000289282	ENST00000687518.1 link	c.354A>G	p.Lys118Lys	splice_region_variant, synonymous_variant	Exon 5 of 5			ENSP00000509222.1		A0A8I5QKQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33208

American (AMR)

AF:

0.00

AC:

AN:

44306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25600

East Asian (EAS)

AF:

0.00

AC:

AN:

39376

South Asian (SAS)

AF:

0.00

AC:

AN:

85260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100874

Other (OTH)

AF:

0.00

AC:

AN:

59706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Benign

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.083

Eigen_PC

Benign

0.056

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

3.7

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

0.0030

B;B

Vest4

0.35

MutPred

0.12

Gain of phosphorylation at N203 (P = 0.0039);Gain of phosphorylation at N203 (P = 0.0039);

MVP

0.17

MPC

0.12

ClinPred

0.81

GERP RS

3.8

Varity_R

0.24

gMVP

0.41

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00046

dbscSNV1_RF

Benign

0.0080

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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rs569008444

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over