dbSNP rs755147720: PRRC2A:p.Pro105Gln (chr6-31624284-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004638.4(PRRC2A):c.314C>A(p.Pro105Gln) 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 1,461,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. P105L) 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: 0.384

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03243044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.314C>A	p.Pro105Gln	missense_variant	Exon 4 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.314C>A	p.Pro105Gln	missense_variant	Exon 4 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.314C>A	p.Pro105Gln	missense_variant	Exon 4 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PRRC2A	ENST00000376033.3 link	c.314C>A	p.Pro105Gln	missense_variant	Exon 4 of 31	1	NM_004638.4	ENSP00000365201.2	P48634-1
PRRC2A	ENST00000376007.8 link	c.314C>A	p.Pro105Gln	missense_variant	Exon 4 of 31	1		ENSP00000365175.4	P48634-1
ENSG00000289282	ENST00000687518.1 link	c.60C>A	p.Ala20Ala	synonymous_variant	Exon 2 of 5			ENSP00000509222.1	A0A8I5QKQ9
PRRC2A	ENST00000469577.5 link	n.159C>A		non_coding_transcript_exon_variant	Exon 2 of 8	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461494

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53090

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111970

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0079

T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.67

N;N

PhyloP100

0.38

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.039

Sift

Benign

0.39

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0020

B;B

Vest4

0.17

MutPred

0.30

Loss of catalytic residue at P105 (P = 0.0154);Loss of catalytic residue at P105 (P = 0.0154);

MVP

0.043

MPC

0.89

ClinPred

0.12

GERP RS

0.76

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.076

gMVP

0.35

Mutation Taster

=87/13

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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rs755147720

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