11-824805-C-T

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.1458C>T(p.Pro486Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,534,204 control chromosomes in the GnomAD database, including 27,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4324 hom., cov: 34)

Exomes 𝑓: 0.18 ( 23211 hom. )

Consequence

PNPLA2
NM_020376.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.511

Publications

15 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 11-824805-C-T is Benign according to our data. Variant chr11-824805-C-T is described in ClinVar as Benign. ClinVar VariationId is 261238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.511 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNPLA2	NM_020376.4 link	c.1458C>T	p.Pro486Pro	synonymous_variant	Exon 10 of 10	ENST00000336615.9	NP_065109.1	Q96AD5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNPLA2	ENST00000336615.9 link	c.1458C>T	p.Pro486Pro	synonymous_variant	Exon 10 of 10	1	NM_020376.4	ENSP00000337701.4		Q96AD5-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32684

AN:

152100

Hom.:

4295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.0917

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.184

GnomAD2 exomes

AF:

0.183

AC:

23580

AN:

128670

AF XY:

0.188

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.0906

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.176

AC:

243905

AN:

1381988

Hom.:

23211

Cov.:

AF XY:

0.178

AC XY:

121455

AN XY:

682088

show subpopulations

African (AFR)

AF:

0.362

AC:

11397

AN:

31474

American (AMR)

AF:

0.106

AC:

3748

AN:

35500

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

3154

AN:

25024

East Asian (EAS)

AF:

0.312

AC:

11133

AN:

35716

South Asian (SAS)

AF:

0.252

AC:

19973

AN:

79150

European-Finnish (FIN)

AF:

0.101

AC:

3389

AN:

33692

Middle Eastern (MID)

AF:

0.101

AC:

572

AN:

5688

European-Non Finnish (NFE)

AF:

0.167

AC:

179824

AN:

1077954

Other (OTH)

AF:

0.185

AC:

10715

AN:

57790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

11520

23040

34560

46080

57600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6786

13572

20358

27144

33930

<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:

0.215

AC:

32749

AN:

152216

Hom.:

4324

Cov.:

AF XY:

0.212

AC XY:

15792

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.356

AC:

14786

AN:

41518

American (AMR)

AF:

0.146

AC:

2239

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

396

AN:

3472

East Asian (EAS)

AF:

0.315

AC:

1629

AN:

5164

South Asian (SAS)

AF:

0.271

AC:

1305

AN:

4822

European-Finnish (FIN)

AF:

0.0917

AC:

974

AN:

10626

Middle Eastern (MID)

AF:

0.113

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.160

AC:

10890

AN:

67982

Other (OTH)

AF:

0.188

AC:

397

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1240

2480

3721

4961

6201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.172

Hom.:

482

Bravo

AF:

0.221

Asia WGS

AF:

0.318

AC:

1105

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neutral lipid storage myopathy

Benign:2

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.7

(source)

DANN

Benign

0.87

PhyloP100

-0.51

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over