rs61735393

Positions:

chr18-2925361-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001375808.2(LPIN2):c.1801G>A(p.Glu601Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 1,614,068 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 100 hom. )

Consequence

LPIN2
NM_001375808.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 3.38

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004709542).

BP6

Variant 18-2925361-C-T is Benign according to our data. Variant chr18-2925361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 138133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2925361-C-T is described in Lovd as [Benign]. Variant chr18-2925361-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00833 (1268/152230) while in subpopulation AMR AF= 0.0186 (285/15296). AF 95% confidence interval is 0.0169. There are 13 homozygotes in gnomad4. There are 617 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN2	NM_001375808.2 linkuse as main transcript	c.1801G>A	p.Glu601Lys	missense_variant	14/20	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1 linkuse as main transcript	c.1801G>A	p.Glu601Lys	missense_variant	14/20		NM_001375808.2	ENSP00000504857.1		Q92539

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1269

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0186

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00892

AC:

2243

AN:

251458

Hom.:

AF XY:

0.00912

AC XY:

1240

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0383

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00304

Gnomad FIN exome

AF:

0.000878

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.00920

AC:

13451

AN:

1461838

Hom.:

100

Cov.:

AF XY:

0.00916

AC XY:

6663

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00230

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.0388

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00328

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00942

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.00833

AC:

1268

AN:

152230

Hom.:

Cov.:

AF XY:

0.00829

AC XY:

617

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.0186

Gnomad4 ASJ

AF:

0.0340

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.00952

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0124

AC:

107

ExAC

AF:

0.00790

AC:

959

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0129

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 19, 2018	This variant is associated with the following publications: (PMID: 27884173, 22995991, 26764160) -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 30, 2017	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	LPIN2: BS1, BS2 -

Majeed syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 30, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Likely benign, criteria provided, single submitter	clinical testing	Genetics and Molecular Pathology, SA Pathology	Dec 18, 2019	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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: HGMD entry based on exitence in disease database and personal communication (http://fmf.igh.cnrs.fr/ISSAID/infevers/detail_mutation.php), reportedly identified in patient(s) with psioriasis, but no inofmration is available. MAF 1.2%. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 31, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.095

Eigen

Benign

-0.071

Eigen_PC

Benign

-0.0066

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.34

Sift

Benign

0.13

Sift4G

Benign

0.35

Polyphen

0.31

Vest4

0.55

MVP

0.57

MPC

0.27

ClinPred

0.0096

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.092

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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