Genetic Variant EBLN2:p.Cys130Tyr (chr3-73062470-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018029.4(EBLN2):c.389G>A(p.Cys130Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EBLN2
NM_018029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.504

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.113473326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN2	NM_018029.4 link	c.389G>A	p.Cys130Tyr	missense_variant	Exon 1 of 1	ENST00000533473.1	NP_060499.3	Q6P2I7
PPP4R2	NM_174907.4 link	c.420-1203G>A		intron_variant	Intron 5 of 8	ENST00000356692.10	NP_777567.1	Q9NY27-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBLN2	ENST00000533473.1 link	c.389G>A	p.Cys130Tyr	missense_variant	Exon 1 of 1	6	NM_018029.4	ENSP00000432104.1		Q6P2I7
PPP4R2	ENST00000356692.10 link	c.420-1203G>A		intron_variant	Intron 5 of 8	1	NM_174907.4	ENSP00000349124.5		Q9NY27-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460694

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726534

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111426

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.389G>A (p.C130Y) alteration is located in exon 1 (coding exon 1) of the EBLN2 gene. This alteration results from a G to A substitution at nucleotide position 389, causing the cysteine (C) at amino acid position 130 to be replaced by a tyrosine (Y). 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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.2

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.057

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.34

M_CAP

Benign

0.0017

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-0.50

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-8.5

REVEL

Benign

0.075

Sift

Benign

0.15

Sift4G

Benign

0.10

Polyphen

0.0

Vest4

0.17

MutPred

0.66

Loss of glycosylation at S125 (P = 0.0934);

MVP

0.072

MPC

0.0037

ClinPred

0.071

GERP RS

-0.57

Varity_R

0.41

gMVP

0.28

Mutation Taster

=97/3

polymorphism

(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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chr3-73062470-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over