Variant 6-31625782-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004638.4(PRRC2A):c.760-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,568,688 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 18 hom. )

Consequence

PRRC2A
NM_004638.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.004927

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.145

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-31625782-C-G is Benign according to our data. Variant chr6-31625782-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3042147.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PRRC2A	NM_004638.4 linkuse as main transcript	c.760-10C>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000376033.3
PRRC2A	NM_080686.3 linkuse as main transcript	c.760-10C>G	splice_polypyrimidine_tract_variant, intron_variant
PRRC2A	XM_047419336.1 linkuse as main transcript	c.760-10C>G	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRRC2A	ENST00000376033.3 linkuse as main transcript	c.760-10C>G	splice_polypyrimidine_tract_variant, intron_variant		1	NM_004638.4	P1	P48634-1
PRRC2A	ENST00000376007.8 linkuse as main transcript	c.760-10C>G	splice_polypyrimidine_tract_variant, intron_variant		1		P1	P48634-1
PRRC2A	ENST00000464890.1 linkuse as main transcript	n.29C>G	non_coding_transcript_exon_variant	1/3	2
PRRC2A	ENST00000469577.5 linkuse as main transcript	n.605-10C>G	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00250

AC:

625

AN:

250364

Hom.:

AF XY:

0.00269

AC XY:

365

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.000623

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00293

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00267

AC:

3778

AN:

1416558

Hom.:

Cov.:

AF XY:

0.00276

AC XY:

1951

AN XY:

707120

show subpopulations

Gnomad4 AFR exome

AF:

0.000340

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00193

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.00353

Gnomad4 FIN exome

AF:

0.00220

Gnomad4 NFE exome

AF:

0.00282

Gnomad4 OTH exome

AF:

0.00221

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152130

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00123

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00201

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PRRC2A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 05, 2019

This variant is classified as likely 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

-0.63

CADD

Benign

8.2

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0049

dbscSNV1_RF

Benign

0.048

SpliceAI score (max)

0.030

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