11-822820-C-CTCTCT

Variant names:

• chr11-822820-C-CTCTCT
• rs10544581
• NM_020376.4:c.696+215_696+216insCTCTT

Variant summary

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

The NM_020376.4(PNPLA2):​c.696+215_696+216insCTCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000030 (0 hom., cov: 0)
• Consequence: PNPLA2 NM_020376.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

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.696+215_696+216insCTCTT		intron	N/A	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.696+214_696+215insTCTCT		intron	N/A	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869283.1		c.1080+214_1080+215insTCTCT		intron	N/A	ENSP00000539342.1
	PNPLA2	ENST00000869284.1		c.696+214_696+215insTCTCT		intron	N/A	ENSP00000539343.1

Frequencies

GnomAD3 genomes AF: 0.0000304 AC: 4 AN: 131480 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000640

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000304 AC: 4 AN: 131480 Hom.: 0 Cov.: 0 AF XY: 0.0000483 AC XY: 3 AN XY: 62072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 36330

American (AMR) AF: 0.00 AC: 0 AN: 12590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3282

East Asian (EAS) AF: 0.00 AC: 0 AN: 4676

South Asian (SAS) AF: 0.00 AC: 0 AN: 4302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.0000640 AC: 4 AN: 62476

Other (OTH) AF: 0.00 AC: 0 AN: 1766

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00215951), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10544581; hg19: chr11-822820;