rs3745012

Variant names:

• chr18-2920290-G-A
• rs3745012
• NM_001375808.2:c.*3C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2920290-G-A
• chr18-2920290-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375808.2(LPIN2):​c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,613,602 control chromosomes in the GnomAD database, including 67,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6311 hom., cov: 32)
  • Exomes 𝑓: 0.28 (61376 hom.)
• Consequence: LPIN2 NM_001375808.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.63
• Publications: 24 publications found

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]

LPIN2 Gene-Disease associations (from GenCC):

• Majeed syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-2920290-G-A is Benign according to our data. Variant chr18-2920290-G-A is described in ClinVar as Benign. ClinVar VariationId is 260433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2	c.*3C>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1	c.*3C>T		3_prime_UTR_variant	Exon 20 of 20		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41955 AN: 151970 Hom.: 6294 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.315 AC: 78969 AN: 250988 AF XY: 0.317

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.599

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.280 AC: 409882 AN: 1461514 Hom.: 61376 Cov.: 35 AF XY: 0.284 AC XY: 206364 AN XY: 727048

African (AFR) AF: 0.224 AC: 7485 AN: 33478

American (AMR) AF: 0.375 AC: 16786 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5735 AN: 26134

East Asian (EAS) AF: 0.587 AC: 23315 AN: 39696

South Asian (SAS) AF: 0.404 AC: 34878 AN: 86250

European-Finnish (FIN) AF: 0.261 AC: 13901 AN: 53298

Middle Eastern (MID) AF: 0.277 AC: 1595 AN: 5752

European-Non Finnish (NFE) AF: 0.259 AC: 288496 AN: 1111796

Other (OTH) AF: 0.293 AC: 17691 AN: 60392

GnomAD4 genome AF: 0.276 AC: 42008 AN: 152088 Hom.: 6311 Cov.: 32 AF XY: 0.281 AC XY: 20863 AN XY: 74350

African (AFR) AF: 0.230 AC: 9553 AN: 41492

American (AMR) AF: 0.344 AC: 5257 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3084 AN: 5156

South Asian (SAS) AF: 0.422 AC: 2034 AN: 4816

European-Finnish (FIN) AF: 0.250 AC: 2651 AN: 10590

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17682 AN: 67960

Other (OTH) AF: 0.294 AC: 621 AN: 2114

Alfa AF: 0.241 Hom.: 3034

Bravo AF: 0.278

Asia WGS AF: 0.502 AC: 1743 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Majeed syndrome Benign:3

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autoinflammatory syndrome Benign:1

Jan 14, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3745012; hg19: chr18-2920288; COSMIC: COSV54428923; COSMIC: COSV54428923;