rs80338806

Variant names:

• chr18-2951103-CAT-C
• rs80338806
• NM_001375808.2:c.540_541delAT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001375808.2(LPIN2):​c.540_541delAT​(p.Cys181fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. T180T) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPIN2 NM_001375808.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:2
• Conservation: PhyloP100: 0.786
• Publications: 5 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

LPIN2-AS1 (HGNC:58311):

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 18-2951103-CAT-C is Pathogenic according to our data. Variant chr18-2951103-CAT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 4909.Status of the report is no_assertion_criteria_provided, 0 stars.

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.540_541delAT	p.Cys181fs	frameshift	Exon 4 of 20	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.540_541delAT	p.Cys181fs	frameshift	Exon 4 of 20	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.540_541delAT	p.Cys181fs	frameshift	Exon 4 of 20	NP_055461.1	Q92539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.540_541delAT	p.Cys181fs	frameshift	Exon 4 of 20	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.540_541delAT	p.Cys181fs	frameshift	Exon 5 of 21	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.540_541delAT	p.Cys181fs	frameshift	Exon 4 of 20	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Majeed syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79
Mutation Taster		=10/190	disease causing (ClinVar)

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: rs80338806; hg19: chr18-2951101;