18-2891168-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.43

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]

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]

ACMG classification

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 GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN2	NM_032048.3	c.1041G>A	p.Lys347=	synonymous_variant	4/8	ENST00000254528.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN2	ENST00000254528.4	c.1041G>A	p.Lys347=	synonymous_variant	4/8	1	NM_032048.3	P1
LPIN2	ENST00000697039.1	c.2547-5734C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00598 AC: 911 AN: 152248 Hom.: 6 Cov.: 32

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.: 18 AF XY: 0.00847 AC XY: 1151 AN XY: 135856

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.: 73 Cov.: 31 AF XY: 0.00910 AC XY: 6618 AN XY: 727236

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.: 6 Cov.: 32 AF XY: 0.00580 AC XY: 432 AN XY: 74516

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.: 7

Bravo AF: 0.00607

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00807

EpiControl AF: 0.00836

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	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

Other links and lift over

dbSNP: rs76428378; hg19: chr18-2891166;