chr6-31622898-G-A

Position:

chr6-31622898-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

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]

PRRC2A links:

PRRC2A (HGNC:):

PRRC2A links:

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	Protein	UniProt
PRRC2A	NM_004638.4 linkuse as main transcript	c.109G>A	p.Ala37Thr	missense_variant	2/31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 linkuse as main transcript	c.109G>A	p.Ala37Thr	missense_variant	2/31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 linkuse as main transcript	c.109G>A	p.Ala37Thr	missense_variant	2/30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRRC2A	ENST00000376033.3 linkuse as main transcript	c.109G>A	p.Ala37Thr	missense_variant	2/31	1	NM_004638.4	ENSP00000365201.2	P48634-1
PRRC2A	ENST00000376007.8 linkuse as main transcript	c.109G>A	p.Ala37Thr	missense_variant	2/31	1		ENSP00000365175.4	P48634-1
PRRC2A	ENST00000469577.5 linkuse as main transcript	n.136-1363G>A		intron_variant		5
ENSG00000291302	ENST00000706625.1 linkuse as main transcript	c.*38G>A		downstream_gene_variant				ENSP00000516471.1	A0A9L9PY68

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

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:

AN:

251398

Hom.:

AF XY:

0.0000515

AC XY:

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:

AN:

1459788

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

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:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

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.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000659

AC:

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

Jul 14, 2021

The 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

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0027

T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.32

N;N

PrimateAI

Uncertain

0.51

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

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.

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