18-2926404-G-T

Variant names:

• chr18-2926404-G-T
• rs3819090
• NM_001375808.2:c.1793+319C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375808.2(LPIN2):​c.1793+319C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,022 control chromosomes in the GnomAD database, including 13,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13727 hom., cov: 32)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2	c.1793+319C>A		intron_variant	Intron 13 of 19	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1	c.1793+319C>A		intron_variant	Intron 13 of 19		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59869 AN: 151904 Hom.: 13687 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.394 AC: 59967 AN: 152022 Hom.: 13727 Cov.: 32 AF XY: 0.397 AC XY: 29476 AN XY: 74312

African (AFR) AF: 0.612 AC: 25376 AN: 41444

American (AMR) AF: 0.395 AC: 6037 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3470

East Asian (EAS) AF: 0.605 AC: 3117 AN: 5154

South Asian (SAS) AF: 0.432 AC: 2078 AN: 4814

European-Finnish (FIN) AF: 0.273 AC: 2887 AN: 10578

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18339 AN: 67978

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.351 Hom.: 7177

Bravo AF: 0.409

Asia WGS AF: 0.543 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.17
DANN	Benign	0.71
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3819090; hg19: chr18-2926402;