11-822820-C-CTCTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_020376.4(PNPLA2):​c.696+215_696+216insCTTT 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 0.0038 (3 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00377 (496/131416) while in subpopulation NFE AF = 0.00516 (322/62452). AF 95% confidence interval is 0.00469. There are 3 homozygotes in GnomAd4. There are 205 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 495 AN: 131442 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.00209

Gnomad AMI AF: 0.00825

Gnomad AMR AF: 0.00398

Gnomad ASJ AF: 0.00335

Gnomad EAS AF: 0.00171

Gnomad SAS AF: 0.00139

Gnomad FIN AF: 0.00162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00515

Gnomad OTH AF: 0.00397

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

GnomAD4 genome AF: 0.00377 AC: 496 AN: 131416 Hom.: 3 Cov.: 0 AF XY: 0.00330 AC XY: 205 AN XY: 62056

African (AFR) AF: 0.00212 AC: 77 AN: 36360

American (AMR) AF: 0.00397 AC: 50 AN: 12580

Ashkenazi Jewish (ASJ) AF: 0.00335 AC: 11 AN: 3282

East Asian (EAS) AF: 0.00172 AC: 8 AN: 4660

South Asian (SAS) AF: 0.00140 AC: 6 AN: 4280

European-Finnish (FIN) AF: 0.00162 AC: 8 AN: 4948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00516 AC: 322 AN: 62452

Other (OTH) AF: 0.00396 AC: 7 AN: 1766

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;