rs7942159

chr11-822622-A-Gchr11-822622-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020376.4(PNPLA2):c.696+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,605,112 control chromosomes in the GnomAD database, including 261,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23921 hom., cov: 33)
  • Exomes 𝑓: 0.56 (237701 hom.)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.71

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-822622-A-G is Benign according to our data. Variant chr11-822622-A-G is described in ClinVar as [Benign]. Clinvar id is 261245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-822622-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA2	NM_020376.4	c.696+16A>G		intron_variant		ENST00000336615.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA2	ENST00000336615.9	c.696+16A>G		intron_variant		1	NM_020376.4	P1
PNPLA2	ENST00000525250.5	n.1302+16A>G		intron_variant, non_coding_transcript_variant		2
PNPLA2	ENST00000531923.1	n.591+16A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84234 AN: 151954 Hom.: 23880 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.554

GnomAD3 exomes AF: 0.538 AC: 134548 AN: 249872 Hom.: 38826 AF XY: 0.519 AC XY: 70291 AN XY: 135308

Gnomad AFR exome AF: 0.516

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.291

Gnomad SAS exome AF: 0.284

Gnomad FIN exome AF: 0.659

Gnomad NFE exome AF: 0.588

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.564 AC: 819950 AN: 1453040 Hom.: 237701 Cov.: 30 AF XY: 0.555 AC XY: 401132 AN XY: 723400

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.686

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.655

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.555 AC: 84328 AN: 152072 Hom.: 23921 Cov.: 33 AF XY: 0.552 AC XY: 41049 AN XY: 74336

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.555

Alfa AF: 0.575 Hom.: 25664

Bravo AF: 0.554

Asia WGS AF: 0.337 AC: 1175 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Neutral lipid storage myopathy Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.2
Dann	Benign	0.81

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: rs7942159; hg19: chr11-822622; COSMIC: COSV60744661; COSMIC: COSV60744661;