11-819748-C-A

Variant names:

• chr11-819748-C-A
• NM_020376.4:c.30C>A
• PNPLA2 p.Ile10Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_020376.4(PNPLA2):​c.30C>A​(p.Ile10Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I10I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PNPLA2 NM_020376.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.47
• 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: G2P, ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.14).
• BP7: Synonymous conserved (PhyloP=2.47 with no splicing effect.

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.30C>A	p.Ile10Ile	synonymous	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.30C>A	p.Ile10Ile	synonymous	Exon 2 of 10	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869283.1		c.30C>A	p.Ile10Ile	synonymous	Exon 2 of 11	ENSP00000539342.1
	PNPLA2	ENST00000869284.1		c.30C>A	p.Ile10Ile	synonymous	Exon 2 of 10	ENSP00000539343.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1356030 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 668348

African (AFR) AF: 0.00 AC: 0 AN: 27530

American (AMR) AF: 0.00 AC: 0 AN: 32136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23920

East Asian (EAS) AF: 0.00 AC: 0 AN: 29974

South Asian (SAS) AF: 0.00 AC: 0 AN: 75322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4778

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060736

Other (OTH) AF: 0.00 AC: 0 AN: 55852

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-819748;