18-2890902-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032048.3(EMILIN2):c.775A>G(p.Met259Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,613,992 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (71 hom.)
• Consequence: EMILIN2 NM_032048.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.88

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017128587).
• BP6: Variant 18-2890902-A-G is Benign according to our data. Variant chr18-2890902-A-G is described in ClinVar as [Benign]. Clinvar id is 791206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMILIN2	NM_032048.3	c.775A>G	p.Met259Val	missense_variant	4/8	ENST00000254528.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMILIN2	ENST00000254528.4	c.775A>G	p.Met259Val	missense_variant	4/8	1	NM_032048.3	P1
LPIN2	ENST00000697039.1	c.2547-5468T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2731 AN: 152212 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00455 AC: 1137 AN: 249964 Hom.: 33 AF XY: 0.00334 AC XY: 452 AN XY: 135400

Gnomad AFR exome AF: 0.0623

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000213

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00182 AC: 2664 AN: 1461662 Hom.: 71 Cov.: 31 AF XY: 0.00158 AC XY: 1146 AN XY: 727112

Gnomad4 AFR exome AF: 0.0618

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000953

Gnomad4 OTH exome AF: 0.00490

GnomAD4 genome AF: 0.0180 AC: 2740 AN: 152330 Hom.: 84 Cov.: 32 AF XY: 0.0173 AC XY: 1286 AN XY: 74492

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00261 Hom.: 19

Bravo AF: 0.0203

ESP6500AA AF: 0.0604 AC: 266

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00559 AC: 679

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	9.1
Dann	Benign	0.45
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.071
Sift	Benign	0.43	T
Sift4G	Benign	0.36	T
Polyphen		0.041	B
Vest4		0.13
MVP		0.15
MPC		0.094
ClinPred		0.0045	T
GERP RS		1.6
Varity_R		0.063
gMVP		0.28

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: rs35267664; hg19: chr18-2890900;