18-2987786-T-G

Variant names:

• chr18-2987786-T-G
• rs3934426
• NM_001375808.2:c.-10+25301A>C

Variant summary

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

The NM_001375808.2(LPIN2):​c.-10+25301A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,128 control chromosomes in the GnomAD database, including 67,913 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 0.94 (67913 hom., cov: 30)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 1 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375808.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	NM_001375808.2	MANE Select	c.-10+25301A>C		intron	N/A	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.-10+25251A>C		intron	N/A	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.-10+23932A>C		intron	N/A	NP_055461.1	Q92539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.-10+25301A>C		intron	N/A	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.-10+23932A>C		intron	N/A	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.-10+25251A>C		intron	N/A	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143331 AN: 152012 Hom.: 67868 Cov.: 30

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.943 AC: 143430 AN: 152128 Hom.: 67913 Cov.: 30 AF XY: 0.944 AC XY: 70176 AN XY: 74366

African (AFR) AF: 0.843 AC: 34957 AN: 41464

American (AMR) AF: 0.970 AC: 14835 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3360 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5174 AN: 5182

South Asian (SAS) AF: 0.943 AC: 4541 AN: 4814

European-Finnish (FIN) AF: 0.996 AC: 10550 AN: 10590

Middle Eastern (MID) AF: 0.925 AC: 270 AN: 292

European-Non Finnish (NFE) AF: 0.983 AC: 66848 AN: 68004

Other (OTH) AF: 0.947 AC: 2000 AN: 2112

Alfa AF: 0.930 Hom.: 19747

Bravo AF: 0.938

Asia WGS AF: 0.967 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		-0.50
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: rs3934426; hg19: chr18-2987784;