rs104895500

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001375808.2(LPIN2):c.1510C>T(p.Leu504Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0032 in 1,606,330 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 14 hom. )

Consequence

LPIN2
NM_001375808.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:8O:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016277522).

BP6

Variant 18-2929105-G-A is Benign according to our data. Variant chr18-2929105-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 97814.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=4, not_provided=1, Likely_benign=5}. Variant chr18-2929105-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00259 (395/152276) while in subpopulation NFE AF = 0.00416 (283/68016). AF 95% confidence interval is 0.00376. There are 2 homozygotes in GnomAd4. There are 172 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2 link	c.1510C>T	p.Leu504Phe	missense_variant	Exon 10 of 20	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1 link	c.1510C>T	p.Leu504Phe	missense_variant	Exon 10 of 20		NM_001375808.2	ENSP00000504857.1		Q92539

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

394

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00227

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00256

AC:

643

AN:

251228

AF XY:

0.00279

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00363

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00326

AC:

4742

AN:

1454054

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

2325

AN XY:

723910

show subpopulations

Gnomad4 AFR exome

AF:

0.000631

AC:

AN:

33306

Gnomad4 AMR exome

AF:

0.00174

AC:

AN:

44710

Gnomad4 ASJ exome

AF:

0.000460

AC:

AN:

26080

Gnomad4 EAS exome

AF:

0.0000758

AC:

AN:

39576

Gnomad4 SAS exome

AF:

0.00230

AC:

198

AN:

86066

Gnomad4 FIN exome

AF:

0.00298

AC:

159

AN:

53332

Gnomad4 NFE exome

AF:

0.00371

AC:

4101

AN:

1105166

Gnomad4 Remaining exome

AF:

0.00273

AC:

164

AN:

60070

Heterozygous variant carriers

230

460

690

920

1150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00259

AC:

395

AN:

152276

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

172

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000794

AC:

0.00079388

AN:

0.00079388

Gnomad4 AMR

AF:

0.00216

AC:

0.00215714

AN:

0.00215714

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288018

AN:

0.000288018

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00331

AC:

0.00331263

AN:

0.00331263

Gnomad4 FIN

AF:

0.00227

AC:

0.00226543

AN:

0.00226543

Gnomad4 NFE

AF:

0.00416

AC:

0.00416079

AN:

0.00416079

Gnomad4 OTH

AF:

0.00190

AC:

0.00189753

AN:

0.00189753

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00293

Hom.:

Bravo

AF:

0.00238

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00454

AC:

ExAC

AF:

0.00264

AC:

321

Asia WGS

AF:

0.000579

AC:

AN:

3470

EpiCase

AF:

0.00360

EpiControl

AF:

0.00308

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:8Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Majeed syndrome

Uncertain:2Benign:2Other:1

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 08, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The LPIN2 c.1510C>T; p.Leu504Phe variant (rs104895500), has been reported in the literature in two individuals with suspected familial Mediterranean fever, but with alternative molecular explanations for disease (Bozgeyik 2020). The variant has also been reported in an individual with psoriasis (see link below). The variant is listed in the ClinVar database (Variation ID: 97814) and is reported in the general population with an overall allele frequency of 0.3% (724/282,640 alleles, including 3 homozygotes) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.675). Due to limited information, the clinical significance of the p.Leu504Phe variant is uncertain at this time. References: Link to variant in Infevers database: https://infevers.umai-montpellier.fr/web/search.php?n=7 Bozgeyik E et al. Next-generation screening of a panel of genes associated with periodic fever syndromes in patients with Familial Mediterranean Fever and their clinical characteristics. Genomics. 2020;112(4):2755-2762. PMID: 32199921. -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Mar 30, 2021

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LPIN2 NM_014646.2 exon 10 p.Leu504Phe (c.1510C>T): This variant has not been reported in the literature but has been reported in 1 individual with psoriasis in the Infevers database (https://infevers.umai-montpellier.fr/web/detail_mutation.php). This variant is present in 0.3% (470/129044) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/18-2929103-G-A). This variant is present in ClinVar (Variation ID:97814). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

not provided

Uncertain:1Benign:4

May 19, 2021

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 15, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LPIN2: PP2, BS2 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Uncertain:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Gene has limited evidence for disease association. Variant is in disease database based on personal communication. Frequency 0.33% -

LPIN2-related disorder

Benign:1

Sep 29, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Autoinflammatory syndrome

Benign:1

Jan 31, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.078

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.16

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0040

Polyphen

0.96

Vest4

0.55

MVP

0.73

MPC

0.72

ClinPred

0.047

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.67

Mutation Taster

=88/12

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

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