rs80338808

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_ModeratePM2PP3_StrongPP5_Moderate

The NM_001375808.2(LPIN2):​c.2327+1G>C variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

LPIN2
NM_001375808.2 splice_donor

Scores

5
1
1
Splicing: ADA: 1.000
2

Clinical Significance

Pathogenic criteria provided, single submitter P:1O:2

Conservation

PhyloP100: 7.52
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.05648458 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 18-2922046-C-G is Pathogenic according to our data. Variant chr18-2922046-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 21519.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LPIN2NM_001375808.2 linkuse as main transcriptc.2327+1G>C splice_donor_variant ENST00000677752.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LPIN2ENST00000677752.1 linkuse as main transcriptc.2327+1G>C splice_donor_variant NM_001375808.2 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Majeed syndrome Pathogenic:1Other:2
not provided, no classification providedliterature onlyUnité médicale des maladies autoinflammatoires, CHRU Montpellier-- -
Pathogenic, criteria provided, single submitterclinical testingBeijing Key Laboratry for Genetics of Birth Defects, Beijing Children's HospitalDec 20, 2020- -
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
33
DANN
Uncertain
1.0
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.98
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
A
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
1.0
Details are displayed if max score is > 0.2
DS_DL_spliceai
1.0
Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs80338808; hg19: chr18-2922044; API