Variant 3-73062250-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018029.4(EBLN2):c.169C>G(p.Pro57Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,599,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

EBLN2
NM_018029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.612

Variant links:

Genes affected

EBLN2 (HGNC:25493): (endogenous Bornavirus like nucleoprotein 2)

EBLN2 links:

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

PPP4R2 links:

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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=0.0043275654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBLN2	NM_018029.4 linkuse as main transcript	c.169C>G	p.Pro57Ala	missense_variant	1/1	ENST00000533473.1	NP_060499.3	Q6P2I7
PPP4R2	NM_174907.4 linkuse as main transcript	c.419+1190C>G		intron_variant		ENST00000356692.10	NP_777567.1	Q9NY27-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBLN2	ENST00000533473.1 linkuse as main transcript	c.169C>G	p.Pro57Ala	missense_variant	1/1	6	NM_018029.4	ENSP00000432104.1		Q6P2I7
PPP4R2	ENST00000356692.10 linkuse as main transcript	c.419+1190C>G		intron_variant		1	NM_174907.4	ENSP00000349124.5		Q9NY27-1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000767

AC:

177

AN:

230814

Hom.:

AF XY:

0.000766

AC XY:

AN XY:

125342

show subpopulations

Gnomad AFR exome

AF:

0.0000680

Gnomad AMR exome

AF:

0.000275

Gnomad ASJ exome

AF:

0.00311

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.000894

GnomAD4 exome

AF:

0.00123

AC:

1778

AN:

1446864

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

889

AN XY:

719570

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.000355

Gnomad4 ASJ exome

AF:

0.00258

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152266

Hom.:

Cov.:

AF XY:

0.000954

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00109

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000482

AC:

ExAC

AF:

0.000662

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

Nov 07, 2022

The c.169C>G (p.P57A) alteration is located in exon 1 (coding exon 1) of the EBLN2 gene. This alteration results from a C to G substitution at nucleotide position 169, causing the proline (P) at amino acid position 57 to be replaced by an alanine (A). 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

0.065

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.041

DANN

Benign

0.58

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0084

LIST_S2

Benign

0.32

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.020

REVEL

Benign

0.052

Sift

Benign

0.43

Sift4G

Benign

0.49

Polyphen

0.0070

Vest4

0.099

MVP

0.095

MPC

0.0047

ClinPred

0.018

GERP RS

-0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.0057

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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