NM_001375808.2:c.2223C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001375808.2(LPIN2):c.2223C>T(p.Ala741Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,974 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 33)

Exomes 𝑓: 0.014 ( 211 hom. )

Consequence

LPIN2
NM_001375808.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -1.37

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

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

LPIN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 18-2922151-G-A is Benign according to our data. Variant chr18-2922151-G-A is described in ClinVar as Benign. ClinVar VariationId is 97815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1737/152282) while in subpopulation NFE AF = 0.0151 (1026/68008). AF 95% confidence interval is 0.0143. There are 13 homozygotes in GnomAd4. There are 790 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2 link	c.2223C>T	p.Ala741Ala	synonymous_variant	Exon 17 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.2223C>T	p.Ala741Ala	synonymous_variant	Exon 17 of 20		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1738

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00762

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00472

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0114

AC:

2850

AN:

250898

AF XY:

0.0117

show subpopulations

Gnomad AFR exome

AF:

0.00702

Gnomad AMR exome

AF:

0.00850

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0141

AC:

20539

AN:

1461692

Hom.:

211

Cov.:

AF XY:

0.0139

AC XY:

10083

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.00783

AC:

262

AN:

33480

American (AMR)

AF:

0.00890

AC:

398

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0419

AC:

1095

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.00261

AC:

225

AN:

86258

European-Finnish (FIN)

AF:

0.00389

AC:

207

AN:

53226

Middle Eastern (MID)

AF:

0.0279

AC:

161

AN:

5768

European-Non Finnish (NFE)

AF:

0.0156

AC:

17301

AN:

1112006

Other (OTH)

AF:

0.0147

AC:

885

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1128

2256

3383

4511

5639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.0114

AC:

1737

AN:

152282

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

790

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00758

AC:

315

AN:

41566

American (AMR)

AF:

0.00889

AC:

136

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00472

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0151

AC:

1026

AN:

68008

Other (OTH)

AF:

0.0147

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

177

265

354

442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0143

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0171

EpiControl

AF:

0.0190

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Majeed syndrome

Benign:3Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 11, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LPIN2: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 27, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Autoinflammatory syndrome

Benign:1

Feb 04, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.62

(source)

DANN

Benign

0.73

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over