18-2937648-A-G

Variant names:

• chr18-2937648-A-G
• rs3826637
• NM_001375808.2:c.1168+44T>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.1168+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,502,338 control chromosomes in the GnomAD database, including 69,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8237 hom., cov: 30)
  • Exomes 𝑓: 0.29 (61760 hom.)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.755
• Publications: 10 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=-0.81).
• BP6: Variant 18-2937648-A-G is Benign according to our data. Variant chr18-2937648-A-G is described in ClinVar as Benign. ClinVar VariationId is 439863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2	c.1168+44T>C		intron_variant	Intron 7 of 19	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1	c.1168+44T>C		intron_variant	Intron 7 of 19		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48276 AN: 151508 Hom.: 8217 Cov.: 30

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.333 AC: 80236 AN: 241056 AF XY: 0.332

Gnomad AFR exome AF: 0.368

Gnomad AMR exome AF: 0.395

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.605

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.293 AC: 395788 AN: 1350714 Hom.: 61760 Cov.: 21 AF XY: 0.296 AC XY: 200584 AN XY: 677886

African (AFR) AF: 0.363 AC: 11367 AN: 31356

American (AMR) AF: 0.391 AC: 17237 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5687 AN: 25442

East Asian (EAS) AF: 0.588 AC: 23050 AN: 39196

South Asian (SAS) AF: 0.412 AC: 34437 AN: 83668

European-Finnish (FIN) AF: 0.278 AC: 13745 AN: 49504

Middle Eastern (MID) AF: 0.287 AC: 1598 AN: 5576

European-Non Finnish (NFE) AF: 0.267 AC: 271184 AN: 1015060

Other (OTH) AF: 0.308 AC: 17483 AN: 56812

GnomAD4 genome AF: 0.319 AC: 48333 AN: 151624 Hom.: 8237 Cov.: 30 AF XY: 0.323 AC XY: 23906 AN XY: 74062

African (AFR) AF: 0.359 AC: 14832 AN: 41306

American (AMR) AF: 0.365 AC: 5555 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3466

East Asian (EAS) AF: 0.606 AC: 3125 AN: 5154

South Asian (SAS) AF: 0.432 AC: 2082 AN: 4816

European-Finnish (FIN) AF: 0.273 AC: 2852 AN: 10452

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18056 AN: 67914

Other (OTH) AF: 0.326 AC: 682 AN: 2094

Alfa AF: 0.275 Hom.: 10584

Bravo AF: 0.324

Asia WGS AF: 0.524 AC: 1821 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Majeed syndrome Benign:1

Jul 03, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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	-0.81
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3826637; hg19: chr18-2937646; COSMIC: COSV107226155; COSMIC: COSV107226155;