11-823809-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020376.4(PNPLA2):c.873C>G(p.Pro291Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,601,182 control chromosomes in the GnomAD database, including 52,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P291P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.21 ( 4059 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48629 hom. )

Consequence

PNPLA2
NM_020376.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.58

Publications

22 publications found

Variant links:

Genes affected

PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]

PNPLA2 Gene-Disease associations (from GenCC):

neutral lipid storage myopathy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet

PNPLA2 links:

ENSG00000255108 (HGNC:):

ENSG00000255108 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-823809-C-G is Benign according to our data. Variant chr11-823809-C-G is described in ClinVar as Benign. ClinVar VariationId is 261248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020376.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	NM_020376.4	MANE Select	c.873C>G	p.Pro291Pro	synonymous	Exon 7 of 10	NP_065109.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.873C>G	p.Pro291Pro	synonymous	Exon 7 of 10	ENSP00000337701.4
PNPLA2	ENST00000529255.1	TSL:1	n.161C>G		non_coding_transcript_exon	Exon 2 of 4
PNPLA2	ENST00000525250.5	TSL:2	n.1585C>G		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32497

AN:

151900

Hom.:

4060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0979

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.273

AC:

60745

AN:

222352

AF XY:

0.289

show subpopulations

Gnomad AFR exome

AF:

0.0939

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.251

AC:

363517

AN:

1449164

Hom.:

48629

Cov.:

AF XY:

0.258

AC XY:

185660

AN XY:

719858

show subpopulations

African (AFR)

AF:

0.0932

AC:

3105

AN:

33302

American (AMR)

AF:

0.196

AC:

8478

AN:

43362

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

10073

AN:

25848

East Asian (EAS)

AF:

0.367

AC:

14375

AN:

39190

South Asian (SAS)

AF:

0.422

AC:

35748

AN:

84784

European-Finnish (FIN)

AF:

0.245

AC:

12340

AN:

50284

Middle Eastern (MID)

AF:

0.376

AC:

2160

AN:

5750

European-Non Finnish (NFE)

AF:

0.236

AC:

261129

AN:

1106736

Other (OTH)

AF:

0.269

AC:

16109

AN:

59908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16734

33468

50202

66936

83670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9028

18056

27084

36112

45140

<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:

0.214

AC:

32482

AN:

152018

Hom.:

4059

Cov.:

AF XY:

0.220

AC XY:

16365

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.0977

AC:

4055

AN:

41494

American (AMR)

AF:

0.207

AC:

3164

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1383

AN:

3472

East Asian (EAS)

AF:

0.391

AC:

2013

AN:

5146

South Asian (SAS)

AF:

0.413

AC:

1994

AN:

4830

European-Finnish (FIN)

AF:

0.262

AC:

2764

AN:

10560

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16299

AN:

67916

Other (OTH)

AF:

0.241

AC:

509

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1278

2557

3835

5114

6392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.184

Hom.:

638

Bravo

AF:

0.206

Asia WGS

AF:

0.354

AC:

1228

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neutral lipid storage myopathy

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

not provided

Benign:2

Jun 25, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.079

(source)

DANN

Benign

0.70

PhyloP100

-2.6

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over