rs144409616

Variant names:

• chr18-2891097-G-A
• rs144409616
• NM_032048.3:c.970G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-2891097-G-A
• chr18-2891097-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032048.3(EMILIN2):​c.970G>A​(p.Ala324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000673 in 1,614,054 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A324P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00053 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (3 hom.)
• Consequence: EMILIN2 NM_032048.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09
• Publications: 2 publications found

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]

LPIN2 Gene-Disease associations (from GenCC):

• Majeed syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014279842).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032048.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMILIN2	NM_032048.3	MANE Select	c.970G>A	p.Ala324Thr	missense	Exon 4 of 8	NP_114437.2	Q9BXX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMILIN2	ENST00000254528.4	TSL:1 MANE Select	c.970G>A	p.Ala324Thr	missense	Exon 4 of 8	ENSP00000254528.3	Q9BXX0
	EMILIN2	ENST00000942047.1		c.970G>A	p.Ala324Thr	missense	Exon 4 of 7	ENSP00000612106.1
	EMILIN2	ENST00000942046.1		c.847G>A	p.Ala283Thr	missense	Exon 3 of 7	ENSP00000612105.1

Frequencies

GnomAD3 genomes AF: 0.000532 AC: 81 AN: 152184 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000633 AC: 159 AN: 251354 AF XY: 0.000618

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.000774

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000688 AC: 1006 AN: 1461870 Hom.: 3 Cov.: 31 AF XY: 0.000733 AC XY: 533 AN XY: 727234

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000510 AC: 44 AN: 86258

European-Finnish (FIN) AF: 0.00125 AC: 67 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000761 AC: 846 AN: 1112012

Other (OTH) AF: 0.000546 AC: 33 AN: 60396

GnomAD4 genome AF: 0.000532 AC: 81 AN: 152184 Hom.: 1 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74342

African (AFR) AF: 0.0000965 AC: 4 AN: 41438

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000643 Hom.: 0

Bravo AF: 0.000400

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000601 AC: 73

EpiCase AF: 0.000273

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.0086
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.055
Sift	Benign	0.14	T
Sift4G	Uncertain	0.012	D
Polyphen		0.091	B
Vest4		0.12
MVP		0.35
MPC		0.13
ClinPred		0.0094	T
GERP RS		5.1
Varity_R		0.085
gMVP		0.34
Mutation Taster		=91/9	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: rs144409616; hg19: chr18-2891095; COSMIC: COSV99039189;