rs1740374107

Variant names:

• chr9-19119663-G-A
• rs1740374107
• NM_001122.4:c.764C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001122.4(PLIN2):​c.764C>T​(p.Ser255Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,442,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PLIN2 NM_001122.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN2	NM_001122.4	MANE Select	c.764C>T	p.Ser255Phe	missense	Exon 6 of 8	NP_001113.2
	PLIN2	NR_038064.2		n.947C>T		non_coding_transcript_exon	Exon 5 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLIN2	ENST00000276914.7	TSL:1 MANE Select	c.764C>T	p.Ser255Phe	missense	Exon 6 of 8	ENSP00000276914.2	Q99541
	PLIN2	ENST00000957811.1		c.791C>T	p.Ser264Phe	missense	Exon 6 of 8	ENSP00000627870.1
	PLIN2	ENST00000907780.1		c.764C>T	p.Ser255Phe	missense	Exon 8 of 10	ENSP00000577839.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442200 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 715504

African (AFR) AF: 0.00 AC: 0 AN: 32802

American (AMR) AF: 0.00 AC: 0 AN: 42444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39412

South Asian (SAS) AF: 0.00 AC: 0 AN: 84212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4606

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100532

Other (OTH) AF: 0.00 AC: 0 AN: 59390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0074	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.1
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.22
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.037	D
Polyphen		0.98	D
Vest4		0.57
MutPred		0.58		Loss of disorder (P = 0.0124)
MVP		0.55
MPC		0.10
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.18
gMVP		0.39
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1740374107; hg19: chr9-19119661;