Variant chr18-2891168-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_032048.3(EMILIN2):c.1041G>A(p.Lys347=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00869 in 1,614,244 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 73 hom. )

Consequence

EMILIN2
NM_032048.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.43

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:

LPIN2 (HGNC:14450): (lipin 2) Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. [provided by RefSeq, Jul 2008]

LPIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 18-2891168-G-A is Benign according to our data. Variant chr18-2891168-G-A is described in ClinVar as [Benign]. Clinvar id is 773335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.43 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMILIN2	NM_032048.3 linkuse as main transcript	c.1041G>A	p.Lys347=	synonymous_variant	4/8	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.1041G>A	p.Lys347=	synonymous_variant	4/8	1	NM_032048.3	ENSP00000254528	P1
LPIN2	ENST00000697039.1 linkuse as main transcript	c.2547-5734C>T		intron_variant				ENSP00000513061

Frequencies

GnomAD3 genomes

AF:

0.00598

AC:

911

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00805

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00803

AC:

2019

AN:

251300

Hom.:

AF XY:

0.00847

AC XY:

1151

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.000815

Gnomad SAS exome

AF:

0.0118

Gnomad FIN exome

AF:

0.00319

Gnomad NFE exome

AF:

0.00848

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00897

AC:

13110

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00910

AC XY:

6618

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00751

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0130

Gnomad4 FIN exome

AF:

0.00363

Gnomad4 NFE exome

AF:

0.00901

Gnomad4 OTH exome

AF:

0.00972

GnomAD4 genome

AF:

0.00599

AC:

912

AN:

152366

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

432

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00581

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0110

Gnomad4 FIN

AF:

0.00292

Gnomad4 NFE

AF:

0.00806

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00920

Hom.:

Bravo

AF:

0.00607

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00807

EpiControl

AF:

0.00836

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	EMILIN2: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

5.2

DANN

Benign

0.57

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