rs17555442

chr18-2922151-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001375808.2(LPIN2):c.2223C>T(p.Ala741=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,974 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., cov: 33)
  • Exomes 𝑓: 0.014 (211 hom.)
• Consequence: LPIN2 NM_001375808.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: -1.37

Genes affected

LPIN2 (HGNC:14450): (lipin 2) Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 18-2922151-G-A is Benign according to our data. Variant chr18-2922151-G-A is described in ClinVar as [Benign]. Clinvar id is 97815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1737/152282) while in subpopulation NFE AF= 0.0151 (1026/68008). AF 95% confidence interval is 0.0143. There are 13 homozygotes in gnomad4. There are 790 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN2	NM_001375808.2	c.2223C>T	p.Ala741=	synonymous_variant	17/20	ENST00000677752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN2	ENST00000677752.1	c.2223C>T	p.Ala741=	synonymous_variant	17/20		NM_001375808.2	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1738 AN: 152164 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00762

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0114 AC: 2850 AN: 250898 Hom.: 42 AF XY: 0.0117 AC XY: 1584 AN XY: 135820

Gnomad AFR exome AF: 0.00702

Gnomad AMR exome AF: 0.00850

Gnomad ASJ exome AF: 0.0409

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.00225

Gnomad FIN exome AF: 0.00342

Gnomad NFE exome AF: 0.0157

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0141 AC: 20539 AN: 1461692 Hom.: 211 Cov.: 33 AF XY: 0.0139 AC XY: 10083 AN XY: 727164

Gnomad4 AFR exome AF: 0.00783

Gnomad4 AMR exome AF: 0.00890

Gnomad4 ASJ exome AF: 0.0419

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00261

Gnomad4 FIN exome AF: 0.00389

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0114 AC: 1737 AN: 152282 Hom.: 13 Cov.: 33 AF XY: 0.0106 AC XY: 790 AN XY: 74472

Gnomad4 AFR AF: 0.00758

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0155 Hom.: 11

Bravo AF: 0.0124

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.0171

EpiControl AF: 0.0190

ClinVar

Significance: Benign

Submissions summary: Benign:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Majeed syndrome Benign:3 Other:1

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
not provided, no classification provided	literature only	Unité médicale des maladies autoinflammatoires, CHRU Montpellier	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 27, 2013

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.62
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17555442; hg19: chr18-2922149;