Variant rs35568725 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001122.4(PLIN2):c.751T>C(p.Ser251Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,603,904 control chromosomes in the GnomAD database, including 2,159 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.040 ( 180 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1979 hom. )

Consequence

PLIN2
NM_001122.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

Variant links:

Genes affected

PLIN2 (HGNC:248): (perilipin 2) The protein encoded by this gene belongs to the perilipin family, members of which coat intracellular lipid storage droplets. This protein is associated with the lipid globule surface membrane material, and maybe involved in development and maintenance of adipose tissue. However, it is not restricted to adipocytes as previously thought, but is found in a wide range of cultured cell lines, including fibroblasts, endothelial and epithelial cells, and tissues, such as lactating mammary gland, adrenal cortex, Sertoli and Leydig cells, and hepatocytes in alcoholic liver cirrhosis, suggesting that it may serve as a marker of lipid accumulation in diverse cell types and diseases. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011]

PLIN2 links:

PLIN2 (HGNC:):

PLIN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040703714).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLIN2	NM_001122.4 linkuse as main transcript	c.751T>C	p.Ser251Pro	missense_variant	6/8	ENST00000276914.7	NP_001113.2	Q99541Q6FHZ7
PLIN2	XM_017014259.3 linkuse as main transcript	c.751T>C	p.Ser251Pro	missense_variant	6/9		XP_016869748.1
PLIN2	NR_038064.2 linkuse as main transcript	n.934T>C		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLIN2	ENST00000276914.7 linkuse as main transcript	c.751T>C	p.Ser251Pro	missense_variant	6/8	1	NM_001122.4	ENSP00000276914.2		Q99541

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6076

AN:

152160

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0260

Gnomad ASJ

AF:

0.0260

Gnomad EAS

AF:

0.00693

Gnomad SAS

AF:

0.0326

Gnomad FIN

AF:

0.0830

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0568

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0406

AC:

10116

AN:

248940

Hom.:

270

AF XY:

0.0418

AC XY:

5620

AN XY:

134576

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0246

Gnomad EAS exome

AF:

0.00615

Gnomad SAS exome

AF:

0.0322

Gnomad FIN exome

AF:

0.0825

Gnomad NFE exome

AF:

0.0522

Gnomad OTH exome

AF:

0.0438

GnomAD4 exome

AF:

0.0494

AC:

71739

AN:

1451626

Hom.:

1979

Cov.:

AF XY:

0.0491

AC XY:

35379

AN XY:

721166

show subpopulations

Gnomad4 AFR exome

AF:

0.0105

Gnomad4 AMR exome

AF:

0.0204

Gnomad4 ASJ exome

AF:

0.0243

Gnomad4 EAS exome

AF:

0.0123

Gnomad4 SAS exome

AF:

0.0312

Gnomad4 FIN exome

AF:

0.0825

Gnomad4 NFE exome

AF:

0.0537

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0399

AC:

6076

AN:

152278

Hom.:

180

Cov.:

AF XY:

0.0413

AC XY:

3076

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0260

Gnomad4 ASJ

AF:

0.0260

Gnomad4 EAS

AF:

0.00694

Gnomad4 SAS

AF:

0.0326

Gnomad4 FIN

AF:

0.0830

Gnomad4 NFE

AF:

0.0568

Gnomad4 OTH

AF:

0.0445

Alfa

AF:

0.0483

Hom.:

342

Bravo

AF:

0.0350

TwinsUK

AF:

0.0472

AC:

175

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.0547

AC:

470

ExAC

AF:

0.0406

AC:

4935

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Benign

0.054

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.12

Sift

Benign

0.065

Sift4G

Benign

0.099

Polyphen

0.11

Vest4

0.32

MPC

0.053

ClinPred

0.041

GERP RS

4.8

Varity_R

0.55

gMVP

0.71

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over