rs66460720

Positions:

• chr11-824987-CTGCA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020376.4(PNPLA2):​c.*130_*133del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 795,266 control chromosomes in the GnomAD database, including 192,035 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38095 hom., cov: 0)
  • Exomes 𝑓: 0.68 (153940 hom.)
• Consequence: PNPLA2 NM_020376.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.441

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-824987-CTGCA-C is Benign according to our data. Variant chr11-824987-CTGCA-C is described in ClinVar as [Benign]. Clinvar id is 306309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA2	NM_020376.4	c.*130_*133del		3_prime_UTR_variant	10/10	ENST00000336615.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA2	ENST00000336615.9	c.*130_*133del		3_prime_UTR_variant	10/10	1	NM_020376.4	P1
PNPLA2	ENST00000529255.1	n.1075_1078del		non_coding_transcript_exon_variant	4/4	1
	ENST00000532946.1	n.307-1128_307-1125del		intron_variant, non_coding_transcript_variant		5
PNPLA2	ENST00000525250.5	n.2499_2502del		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.706 AC: 106744 AN: 151158 Hom.: 38033 Cov.: 0

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.684

GnomAD3 exomes AF: 0.667 AC: 87229 AN: 130820 Hom.: 29900 AF XY: 0.649 AC XY: 46247 AN XY: 71246

Gnomad AFR exome AF: 0.717

Gnomad AMR exome AF: 0.770

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.590

Gnomad SAS exome AF: 0.484

Gnomad FIN exome AF: 0.729

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.684 AC: 440732 AN: 643988 Hom.: 153940 AF XY: 0.673 AC XY: 230348 AN XY: 342432

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.718

Gnomad4 OTH exome AF: 0.672

GnomAD4 genome AF: 0.706 AC: 106864 AN: 151278 Hom.: 38095 Cov.: 0 AF XY: 0.701 AC XY: 51753 AN XY: 73880

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.688

Alfa AF: 0.693 Hom.: 6722

Bravo AF: 0.710

Asia WGS AF: 0.595 AC: 2070 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neutral lipid storage myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 22, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs398054898; hg19: chr11-824987;