Genetic Variant LPIN2:c.590+3024G>A (chr18-2948031-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375808.2(LPIN2):c.590+3024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,196 control chromosomes in the GnomAD database, including 1,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1721 hom., cov: 32)

Consequence

LPIN2
NM_001375808.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.669

Publications

30 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

LPIN2 links:

LPIN2-AS1 (HGNC:58311):

LPIN2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375808.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPIN2	NM_001375808.2	MANE Select	c.590+3024G>A	intron	N/A	NP_001362737.1	Q92539
LPIN2	NM_001375809.1		c.590+3024G>A	intron	N/A	NP_001362738.1	Q92539
LPIN2	NM_014646.2		c.590+3024G>A	intron	N/A	NP_055461.1	Q92539

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPIN2	ENST00000677752.1	MANE Select	c.590+3024G>A	intron	N/A	ENSP00000504857.1	Q92539
LPIN2	ENST00000261596.9	TSL:1	c.590+3024G>A	intron	N/A	ENSP00000261596.4	Q92539
LPIN2	ENST00000697040.1		c.590+3024G>A	intron	N/A	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18690

AN:

152078

Hom.:

1716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0610

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.123

AC:

18715

AN:

152196

Hom.:

1721

Cov.:

AF XY:

0.127

AC XY:

9451

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0609

AC:

2532

AN:

41554

American (AMR)

AF:

0.191

AC:

2926

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

418

AN:

3466

East Asian (EAS)

AF:

0.472

AC:

2439

AN:

5166

South Asian (SAS)

AF:

0.231

AC:

1115

AN:

4826

European-Finnish (FIN)

AF:

0.119

AC:

1259

AN:

10590

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7630

AN:

67988

Other (OTH)

AF:

0.149

AC:

314

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

797

1594

2390

3187

3984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.126

Hom.:

3884

Bravo

AF:

0.126

Asia WGS

AF:

0.319

AC:

1108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.3

(source)

DANN

Benign

0.76

PhyloP100

-0.67

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over