dbSNP rs61735393: LPIN2:p.Glu601Lys (chr18-2925361-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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. 12/21 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

Publications

12 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 138133.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
LPIN2	NM_001375808.2	MANE Select	c.1801G>A	p.Glu601Lys	missense	Exon 14 of 20	NP_001362737.1	Q92539
LPIN2	NM_001375809.1		c.1801G>A	p.Glu601Lys	missense	Exon 14 of 20	NP_001362738.1	Q92539
LPIN2	NM_014646.2		c.1801G>A	p.Glu601Lys	missense	Exon 14 of 20	NP_055461.1	Q92539

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LPIN2	ENST00000677752.1	MANE Select	c.1801G>A	p.Glu601Lys	missense	Exon 14 of 20	ENSP00000504857.1	Q92539
LPIN2	ENST00000261596.9	TSL:1	c.1801G>A	p.Glu601Lys	missense	Exon 15 of 21	ENSP00000261596.4	Q92539
LPIN2	ENST00000697040.1		c.1801G>A	p.Glu601Lys	missense	Exon 14 of 20	ENSP00000513062.1	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

GnomAD2 exomes

AF:

0.00892

AC:

2243

AN:

251458

AF XY:

0.00912

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 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

African (AFR)

AF:

0.00230

AC:

AN:

33480

American (AMR)

AF:

0.0126

AC:

565

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0388

AC:

1014

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00328

AC:

283

AN:

86256

European-Finnish (FIN)

AF:

0.00137

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0373

AC:

215

AN:

5764

European-Non Finnish (NFE)

AF:

0.00942

AC:

10475

AN:

1111976

Other (OTH)

AF:

0.0124

AC:

746

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

829

1658

2487

3316

4145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.00833

AC:

1268

AN:

152230

Hom.:

Cov.:

AF XY:

0.00829

AC XY:

617

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00212

AC:

AN:

41548

American (AMR)

AF:

0.0186

AC:

285

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00229

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

701

AN:

68002

Other (OTH)

AF:

0.0161

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0109

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Majeed syndrome (4)

not specified (3)

Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

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

PhyloP100

3.4

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

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over