NM_001375808.2:c.2223C>A

Variant names:

• chr18-2922151-G-T
• rs17555442
• NM_001375808.2:c.2223C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001375808.2(LPIN2):​c.2223C>A​(p.Ala741Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A741A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LPIN2 NM_001375808.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	NM_001375808.2	MANE Select	c.2223C>A	p.Ala741Ala	synonymous	Exon 17 of 20	NP_001362737.1
	LPIN2	NM_001375809.1		c.2223C>A	p.Ala741Ala	synonymous	Exon 17 of 20	NP_001362738.1
	LPIN2	NM_014646.2		c.2223C>A	p.Ala741Ala	synonymous	Exon 17 of 20	NP_055461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.2223C>A	p.Ala741Ala	synonymous	Exon 17 of 20	ENSP00000504857.1
	LPIN2	ENST00000261596.9	TSL:1	c.2223C>A	p.Ala741Ala	synonymous	Exon 18 of 21	ENSP00000261596.4
	LPIN2	ENST00000697040.1		c.2223C>A	p.Ala741Ala	synonymous	Exon 17 of 20	ENSP00000513062.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.14
DANN	Benign	0.67
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs17555442; hg19: chr18-2922149;