11-822820-C-CTCTT

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA2	NM_020376.4	c.696+215_696+216insCTTT		intron_variant		ENST00000336615.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA2	ENST00000336615.9	c.696+215_696+216insCTTT		intron_variant		1	NM_020376.4	P1
PNPLA2	ENST00000525250.5	n.1302+215_1302+216insCTTT		intron_variant, non_coding_transcript_variant		2
PNPLA2	ENST00000531923.1	n.591+215_591+216insCTTT		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00397

Gnomad4 ASJ AF: 0.00335

Gnomad4 EAS AF: 0.00172

Gnomad4 SAS AF: 0.00140

Gnomad4 FIN AF: 0.00162

Gnomad4 NFE AF: 0.00516

Gnomad4 OTH AF: 0.00396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10544581; hg19: chr11-822820;