Variant 20-5115453-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_182649.2(PCNA):c.702C>G(p.Pro234Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,998 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 28 hom. )

Consequence

PCNA
NM_182649.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00100

Variant links:

Genes affected

PCNA (HGNC:8729): (proliferating cell nuclear antigen) The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ubiquitinated and is involved in the RAD6-dependent DNA repair pathway. Two transcript variants encoding the same protein have been found for this gene. Pseudogenes of this gene have been described on chromosome 4 and on the X chromosome. [provided by RefSeq, Jul 2008]

PCNA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 20-5115453-G-C is Benign according to our data. Variant chr20-5115453-G-C is described in ClinVar as [Benign]. Clinvar id is 786675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-5115453-G-C is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNA	NM_182649.2 linkuse as main transcript	c.702C>G	p.Pro234Pro	synonymous_variant	5/6	ENST00000379143.10	NP_872590.1	P12004
PCNA	NM_002592.2 linkuse as main transcript	c.702C>G	p.Pro234Pro	synonymous_variant	6/7		NP_002583.1	P12004

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNA	ENST00000379143.10 linkuse as main transcript	c.702C>G	p.Pro234Pro	synonymous_variant	5/6	1	NM_182649.2	ENSP00000368438.5		P12004
PCNA	ENST00000379160.3 linkuse as main transcript	c.702C>G	p.Pro234Pro	synonymous_variant	6/7	5		ENSP00000368458.3		P12004

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00275

AC:

691

AN:

251352

Hom.:

AF XY:

0.00340

AC XY:

462

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00208

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00289

AC:

4231

AN:

1461714

Hom.:

Cov.:

AF XY:

0.00314

AC XY:

2284

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0125

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00160

AC:

244

AN:

152284

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0129

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00137

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00218

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PCNA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

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

-0.67

CADD

Benign

5.4

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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