Variant 18-2847303-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032048.3(EMILIN2):c.115C>T(p.Arg39Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000038 in 1,316,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

EMILIN2
NM_032048.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.106

Variant links:

Genes affected

EMILIN2 (HGNC:19881): (elastin microfibril interfacer 2) Predicted to enable extracellular matrix constituent conferring elasticity. Predicted to be involved in cell adhesion. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EMILIN2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34729838).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMILIN2	NM_032048.3 linkuse as main transcript	c.115C>T	p.Arg39Trp	missense_variant	1/8	ENST00000254528.4	NP_114437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMILIN2	ENST00000254528.4 linkuse as main transcript	c.115C>T	p.Arg39Trp	missense_variant	1/8	1	NM_032048.3	ENSP00000254528	P1
	ENST00000693116.1 linkuse as main transcript	n.77+471G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000258

AC:

AN:

1164120

Hom.:

Cov.:

AF XY:

0.00000356

AC XY:

AN XY:

562324

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000207

Gnomad4 OTH exome

AF:

0.0000213

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.115C>T (p.R39W) alteration is located in exon 1 (coding exon 1) of the EMILIN2 gene. This alteration results from a C to T substitution at nucleotide position 115, causing the arginine (R) at amino acid position 39 to be replaced by a tryptophan (W). 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

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.95

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.088

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.42

MutPred

0.36

Loss of disorder (P = 0.0067);

MVP

0.44

MPC

0.48

ClinPred

0.99

GERP RS

1.8

Varity_R

0.16

gMVP

0.59

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