chr3-73062289-C-G

Variant names:

• chr3-73062289-C-G
• rs370588670
• NM_018029.4:c.208C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018029.4(EBLN2):​c.208C>G​(p.Leu70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L70F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBLN2 NM_018029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 0 publications found

Genes affected

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

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]

ACMG classification

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=0.08808482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN2	NM_018029.4	c.208C>G	p.Leu70Val	missense_variant	Exon 1 of 1	ENST00000533473.1	NP_060499.3
PPP4R2	NM_174907.4	c.419+1229C>G		intron_variant	Intron 5 of 8	ENST00000356692.10	NP_777567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBLN2	ENST00000533473.1	c.208C>G	p.Leu70Val	missense_variant	Exon 1 of 1	6	NM_018029.4	ENSP00000432104.1
PPP4R2	ENST00000356692.10	c.419+1229C>G		intron_variant	Intron 5 of 8	1	NM_174907.4	ENSP00000349124.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.1
DANN	Benign	0.93
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.30
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.027
Sift	Uncertain	0.027	D
Sift4G	Benign	0.071	T
Polyphen		0.39	B
Vest4		0.058
MutPred		0.62		Gain of glycosylation at S68 (P = 0.044);
MVP		0.081
MPC		0.013
ClinPred		0.094	T
GERP RS		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.0039
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs370588670; hg19: chr3-73111440;