rs66460720

Variant names:

• chr11-824987-CTGCA-C
• rs398054898
• NM_020376.4:c.*130_*133delTGCA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_020376.4(PNPLA2):​c.*130_*133delTGCA 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
• Publications: 5 publications found

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, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ENSG00000255108 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	NM_020376.4	MANE Select	c.*130_*133delTGCA		3_prime_UTR	Exon 10 of 10	NP_065109.1	Q96AD5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.*130_*133delTGCA		3_prime_UTR	Exon 10 of 10	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000529255.1	TSL:1	n.1075_1078delTGCA		non_coding_transcript_exon	Exon 4 of 4
	PNPLA2	ENST00000869283.1		c.*130_*133delTGCA		3_prime_UTR	Exon 11 of 11	ENSP00000539342.1

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

GnomAD2 exomes AF: 0.667 AC: 87229 AN: 130820 AF XY: 0.649

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 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

African (AFR) AF: 0.714 AC: 12307 AN: 17242

American (AMR) AF: 0.764 AC: 25944 AN: 33968

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 10947 AN: 20108

East Asian (EAS) AF: 0.633 AC: 20305 AN: 32074

South Asian (SAS) AF: 0.484 AC: 30821 AN: 63614

European-Finnish (FIN) AF: 0.726 AC: 24092 AN: 33168

Middle Eastern (MID) AF: 0.551 AC: 2345 AN: 4256

European-Non Finnish (NFE) AF: 0.718 AC: 291476 AN: 406088

Other (OTH) AF: 0.672 AC: 22495 AN: 33470

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

African (AFR) AF: 0.716 AC: 29519 AN: 41226

American (AMR) AF: 0.737 AC: 11225 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1844 AN: 3462

East Asian (EAS) AF: 0.605 AC: 3077 AN: 5082

South Asian (SAS) AF: 0.499 AC: 2405 AN: 4818

European-Finnish (FIN) AF: 0.711 AC: 7449 AN: 10470

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49039 AN: 67692

Other (OTH) AF: 0.688 AC: 1446 AN: 2102

Alfa AF: 0.693 Hom.: 6722

Bravo AF: 0.710

Asia WGS AF: 0.595 AC: 2070 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neutral lipid storage myopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs398054898; hg19: chr11-824987; COSMIC: COSV60743763; COSMIC: COSV60743763;