rs35568725

chr9-19119676-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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]

ACMG classification

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	UniProt
PLIN2	NM_001122.4	c.751T>C	p.Ser251Pro	missense_variant	6/8	ENST00000276914.7
PLIN2	XM_017014259.3	c.751T>C	p.Ser251Pro	missense_variant	6/9
PLIN2	NR_038064.2	n.934T>C		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLIN2	ENST00000276914.7	c.751T>C	p.Ser251Pro	missense_variant	6/8	1	NM_001122.4	P1

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6076 AN: 152160 Hom.: 180 Cov.: 32

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

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.: 30 AF XY: 0.0491 AC XY: 35379 AN XY: 721166

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.: 32 AF XY: 0.0413 AC XY: 3076 AN XY: 74450

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: 63

ESP6500EA AF: 0.0547 AC: 470

ExAC AF: 0.0406 AC: 4935

Asia WGS AF: 0.0210 AC: 73 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	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.054
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.12
Sift	Benign	0.065	T
Sift4G	Benign	0.099	T
Polyphen		0.11	B
Vest4		0.32
MPC		0.053
ClinPred		0.041	T
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

Other links and lift over

dbSNP: rs35568725; hg19: chr9-19119674; COSMIC: COSV52804582; COSMIC: COSV52804582;