rs373758040

Variant names:

• chr18-2931373-C-A
• rs373758040
• NM_001375808.2:c.1339G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2931373-C-A
• chr18-2931373-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001375808.2(LPIN2):​c.1339G>T​(p.Val447Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V447M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: LPIN2 NM_001375808.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.45
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2	c.1339G>T	p.Val447Leu	missense_variant	Exon 9 of 20	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1	c.1339G>T	p.Val447Leu	missense_variant	Exon 9 of 20		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1460548 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 726414

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 85960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111460

Other (OTH) AF: 0.0000331 AC: 2 AN: 60356

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.61
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.37
Sift	Benign	0.18	T
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.55
MutPred		0.14		Loss of catalytic residue at V447 (P = 0.2034);
MVP		0.45
MPC		0.77
ClinPred		0.96	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.22
gMVP		0.32
Mutation Taster		=39/61	disease causing

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: rs373758040; hg19: chr18-2931371;