chr6-31625488-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000687518.1(ENSG00000289282):c.382G>T(p.Ala128Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 1,588,870 control chromosomes in the GnomAD database, including 1,355 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A128V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.030 ( 99 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1256 hom. )

Consequence

ENSG00000289282
ENST00000687518.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.999

Variant links:

Genes affected

ENSG00000289282 (HGNC:):

ENSG00000289282 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 6-31625488-G-T is Benign according to our data. Variant chr6-31625488-G-T is described in ClinVar as [Benign]. Clinvar id is 3056017.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0301 (4589/152286) while in subpopulation NFE AF= 0.0462 (3141/68008). AF 95% confidence interval is 0.0448. There are 99 homozygotes in gnomad4. There are 2142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 99 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2A	NM_004638.4 link	c.636G>T	p.Gly212Gly	synonymous_variant	Exon 7 of 31	ENST00000376033.3	NP_004629.3	P48634-1A0A1U9X974
PRRC2A	NM_080686.3 link	c.636G>T	p.Gly212Gly	synonymous_variant	Exon 7 of 31		NP_542417.2	P48634-1A0A1U9X974
PRRC2A	XM_047419336.1 link	c.636G>T	p.Gly212Gly	synonymous_variant	Exon 7 of 30		XP_047275292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289282	ENST00000687518.1 link	c.382G>T	p.Ala128Ser	missense_variant	Exon 5 of 5			ENSP00000509222.1		A0A8I5QKQ9
PRRC2A	ENST00000376033.3 link	c.636G>T	p.Gly212Gly	synonymous_variant	Exon 7 of 31	1	NM_004638.4	ENSP00000365201.2		P48634-1

Frequencies

GnomAD3 genomes

AF:

0.0302

AC:

4589

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00671

Gnomad AMI

AF:

0.0516

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00423

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0438

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0319

AC:

7545

AN:

236408

Hom.:

171

AF XY:

0.0332

AC XY:

4205

AN XY:

126714

show subpopulations

Gnomad AFR exome

AF:

0.00532

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00453

Gnomad SAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.0470

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0315

GnomAD4 exome

AF:

0.0395

AC:

56800

AN:

1436584

Hom.:

1256

Cov.:

AF XY:

0.0392

AC XY:

27850

AN XY:

710642

show subpopulations

Gnomad4 AFR exome

AF:

0.00530

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.00562

Gnomad4 SAS exome

AF:

0.0207

Gnomad4 FIN exome

AF:

0.0481

Gnomad4 NFE exome

AF:

0.0446

Gnomad4 OTH exome

AF:

0.0344

GnomAD4 genome

AF:

0.0301

AC:

4589

AN:

152286

Hom.:

Cov.:

AF XY:

0.0288

AC XY:

2142

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00669

Gnomad4 AMR

AF:

0.0278

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00424

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.0438

Gnomad4 NFE

AF:

0.0462

Gnomad4 OTH

AF:

0.0308

Alfa

AF:

0.0376

Hom.:

187

Bravo

AF:

0.0271

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Feb 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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