rs150806357

Positions:

chr18-2925286-G-A

Variant summary

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

The NM_001375808.2(LPIN2):c.1876C>T(p.Pro626Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,178 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 18 hom. )

Consequence

LPIN2
NM_001375808.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.45

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=0.003803581).

BP6

Variant 18-2925286-G-A is Benign according to our data. Variant chr18-2925286-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 378095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-2925286-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00111 (169/152300) while in subpopulation SAS AF= 0.00994 (48/4828). AF 95% confidence interval is 0.0077. There are 2 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN2	NM_001375808.2 link	c.1876C>T	p.Pro626Ser	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 link	c.1876C>T	p.Pro626Ser	missense_variant	14/20		NM_001375808.2	ENSP00000504857.1		Q92539

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00264

AC:

664

AN:

251486

Hom.:

AF XY:

0.00318

AC XY:

432

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00229

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00191

AC:

2787

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

1650

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152300

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00994

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.000948

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00297

AC:

361

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2021	This variant is associated with the following publications: (PMID: 28750028, 26386126) -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	LPIN2: BP4, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Majeed syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
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). 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 rule this variant out of causing disease. Therefore, this variant is classified as benign. -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 06, 2023	- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.26

DEOGEN2

Benign

0.049

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.36

REVEL

Benign

0.15

Sift

Benign

0.65

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.27

MVP

0.29

MPC

0.24

ClinPred

0.0096

GERP RS

1.8

Varity_R

0.016

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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