11-822820-C-CTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020376.4(PNPLA2):c.696+215_696+216insCTT 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 0.39 (12903 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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.394 AC: 51935 AN: 131654 Hom.: 12903 Cov.: 0

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.394 AC: 51922 AN: 131628 Hom.: 12903 Cov.: 0 AF XY: 0.383 AC XY: 23821 AN XY: 62172

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.414

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;