3-73062217-T-G

Variant names:

• chr3-73062217-T-G
• rs2231924
• NM_018029.4:c.136T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018029.4(EBLN2):​c.136T>G​(p.Ser46Ala) 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EBLN2 NM_018029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 30 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041369557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN2	NM_018029.4	c.136T>G	p.Ser46Ala	missense_variant	Exon 1 of 1	ENST00000533473.1	NP_060499.3
PPP4R2	NM_174907.4	c.419+1157T>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.136T>G	p.Ser46Ala	missense_variant	Exon 1 of 1	6	NM_018029.4	ENSP00000432104.1
PPP4R2	ENST00000356692.10	c.419+1157T>G		intron_variant	Intron 5 of 8	1	NM_174907.4	ENSP00000349124.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.2
DANN	Benign	0.40
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.099	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.0090
Sift	Benign	0.066	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.045
MutPred		0.28		Gain of glycosylation at S49 (P = 0.0062);
MVP		0.067
MPC		0.0050
ClinPred		0.042	T
GERP RS		-0.46
Varity_R		0.075
gMVP		0.0053
Mutation Taster		=96/4	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: rs2231924; hg19: chr3-73111368;