11-819599-C-G

Variant names:

• chr11-819599-C-G
• rs966083119
• NM_020376.4:c.-120C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020376.4(PNPLA2):​c.-120C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000885 in 1,129,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: PNPLA2 NM_020376.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

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.-120C>G		5_prime_UTR	Exon 2 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.-120C>G		5_prime_UTR	Exon 2 of 10	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869283.1		c.-120C>G		5_prime_UTR	Exon 2 of 11	ENSP00000539342.1
	PNPLA2	ENST00000869284.1		c.-120C>G		5_prime_UTR	Exon 2 of 10	ENSP00000539343.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 8.85e-7 AC: 1 AN: 1129722 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 545424

African (AFR) AF: 0.00 AC: 0 AN: 22266

American (AMR) AF: 0.00 AC: 0 AN: 8498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15546

East Asian (EAS) AF: 0.00 AC: 0 AN: 25926

South Asian (SAS) AF: 0.00 AC: 0 AN: 45506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3194

European-Non Finnish (NFE) AF: 0.00000107 AC: 1 AN: 934406

Other (OTH) AF: 0.00 AC: 0 AN: 46346

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.58
PhyloP100		-0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs966083119; hg19: chr11-819599;