rs11554663

Variant names:

• chr11-824428-G-A
• rs11554663
• NM_020376.4:c.1167G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-824428-G-A
• chr11-824428-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020376.4(PNPLA2):​c.1167G>A​(p.Leu389Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,492 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. Synonymous variant affecting the same amino acid position (i.e. L389L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PNPLA2 NM_020376.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 9 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, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000255108 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.015 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.1167G>A	p.Leu389Leu	synonymous	Exon 9 of 10	NP_065109.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.1167G>A	p.Leu389Leu	synonymous	Exon 9 of 10	ENSP00000337701.4
	PNPLA2	ENST00000529255.1	TSL:1	n.597G>A		non_coding_transcript_exon	Exon 3 of 4
	PNPLA2	ENST00000869283.1		c.1551G>A	p.Leu517Leu	synonymous	Exon 10 of 11	ENSP00000539342.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402492 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 692344

African (AFR) AF: 0.00 AC: 0 AN: 31942

American (AMR) AF: 0.00 AC: 0 AN: 36300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25200

East Asian (EAS) AF: 0.00 AC: 0 AN: 36076

South Asian (SAS) AF: 0.00 AC: 0 AN: 79596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081742

Other (OTH) AF: 0.00 AC: 0 AN: 58184

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.83
PhyloP100		-0.015

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: rs11554663; hg19: chr11-824428;