rs886038654

Positions:

• chr11-824805-CT-TC

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP6_Very_Strong BP7

The NM_020376.4(PNPLA2):​c.1458_1459delinsTC​(p.ProLeu486=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P486P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PNPLA2 NM_020376.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.511

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-824805-CT-TC is Benign according to our data. Variant chr11-824805-CT-TC is described in ClinVar as [Likely_benign]. Clinvar id is 261237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.511 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNPLA2	NM_020376.4	c.1458_1459delinsTC	p.ProLeu486=	synonymous_variant	10/10	ENST00000336615.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNPLA2	ENST00000336615.9	c.1458_1459delinsTC	p.ProLeu486=	synonymous_variant	10/10	1	NM_020376.4	P1
PNPLA2	ENST00000529255.1	n.888_889delinsTC		non_coding_transcript_exon_variant	4/4	1
	ENST00000532946.1	n.307-943_307-942delinsGA		intron_variant, non_coding_transcript_variant		5
PNPLA2	ENST00000525250.5	n.2312_2313delinsTC		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Neutral lipid storage myopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 05, 2023

- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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: rs886038654; hg19: chr11-824805;