6-31625488-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.0319

AC:

7545

AN:

236408

AF XY:

0.0332

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 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

African (AFR)

AF:

0.00530

AC:

175

AN:

33004

American (AMR)

AF:

0.0175

AC:

760

AN:

43532

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

392

AN:

24650

East Asian (EAS)

AF:

0.00562

AC:

221

AN:

39344

South Asian (SAS)

AF:

0.0207

AC:

1714

AN:

82842

European-Finnish (FIN)

AF:

0.0481

AC:

2528

AN:

52578

Middle Eastern (MID)

AF:

0.0143

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0446

AC:

48888

AN:

1095716

Other (OTH)

AF:

0.0344

AC:

2041

AN:

59250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3119

6237

9356

12474

15593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0301

AC:

4589

AN:

152286

Hom.:

Cov.:

AF XY:

0.0288

AC XY:

2142

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00669

AC:

278

AN:

41562

American (AMR)

AF:

0.0278

AC:

425

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3468

East Asian (EAS)

AF:

0.00424

AC:

AN:

5188

South Asian (SAS)

AF:

0.0180

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0438

AC:

465

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0462

AC:

3141

AN:

68008

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

225

450

676

901

1126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0400

Hom.:

399

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

(source)

DANN

Benign

0.84

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism (auto)

(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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6-31625488-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over