Variant 11-822588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020376.4(PNPLA2):c.678C>T(p.Leu226Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,613,588 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 252 hom., cov: 33)

Exomes 𝑓: 0.022 ( 2042 hom. )

Consequence

PNPLA2
NM_020376.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0430

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 links:

PNPLA2 (HGNC:):

PNPLA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 11-822588-C-T is Benign according to our data. Variant chr11-822588-C-T is described in ClinVar as [Benign]. Clinvar id is 261243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.043 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNPLA2	NM_020376.4 linkuse as main transcript	c.678C>T	p.Leu226Leu	synonymous_variant	5/10	ENST00000336615.9	NP_065109.1	Q96AD5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PNPLA2	ENST00000336615.9 linkuse as main transcript	c.678C>T	p.Leu226Leu	synonymous_variant	5/10	1	NM_020376.4	ENSP00000337701.4	Q96AD5-1
PNPLA2	ENST00000525250.5 linkuse as main transcript	n.1284C>T		non_coding_transcript_exon_variant	3/6	2
PNPLA2	ENST00000531923.1 linkuse as main transcript	n.573C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4941

AN:

152226

Hom.:

252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0447

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0356

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00729

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0432

AC:

10849

AN:

251198

Hom.:

860

AF XY:

0.0454

AC XY:

6167

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.00712

Gnomad OTH exome

AF:

0.0295

GnomAD4 exome

AF:

0.0220

AC:

32154

AN:

1461244

Hom.:

2042

Cov.:

AF XY:

0.0246

AC XY:

17915

AN XY:

726966

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.120

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.00687

Gnomad4 OTH exome

AF:

0.0348

GnomAD4 genome

AF:

0.0326

AC:

4960

AN:

152344

Hom.:

252

Cov.:

AF XY:

0.0357

AC XY:

2658

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0451

Gnomad4 AMR

AF:

0.0355

Gnomad4 ASJ

AF:

0.0207

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00729

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.165

AC:

574

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00771

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.4

DANN

Benign

0.75

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over