18-2948031-C-T

Variant names:

• chr18-2948031-C-T
• rs10460009
• NM_001375808.2:c.590+3024G>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.590+3024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,196 control chromosomes in the GnomAD database, including 1,721 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 0.12 (1721 hom., cov: 32)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 30 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

ENSG00000265907 (HGNC:58311):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2	c.590+3024G>A		intron_variant	Intron 4 of 19	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1	c.590+3024G>A		intron_variant	Intron 4 of 19		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18690 AN: 152078 Hom.: 1716 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.123 AC: 18715 AN: 152196 Hom.: 1721 Cov.: 32 AF XY: 0.127 AC XY: 9451 AN XY: 74408

African (AFR) AF: 0.0609 AC: 2532 AN: 41554

American (AMR) AF: 0.191 AC: 2926 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2439 AN: 5166

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7630 AN: 67988

Other (OTH) AF: 0.149 AC: 314 AN: 2112

Alfa AF: 0.126 Hom.: 3884

Bravo AF: 0.126

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.76
PhyloP100		-0.67
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: rs10460009; hg19: chr18-2948029;