2-11819857-A-G

Position:

• chr2-11819857-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001349206.2(LPIN1):​c.2517+259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 152,276 control chromosomes in the GnomAD database, including 457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.055 (457 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190

Genes affected

LPIN1 (HGNC:13345): (lipin 1) This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]

LPIN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-11819857-A-G is Benign according to our data. Variant chr2-11819857-A-G is described in ClinVar as [Benign]. Clinvar id is 1257812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.2517+259A>G		intron_variant		ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.2517+259A>G		intron_variant			NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8365 AN: 152158 Hom.: 455 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0611

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

GnomAD4 genome AF: 0.0550 AC: 8378 AN: 152276 Hom.: 457 Cov.: 32 AF XY: 0.0556 AC XY: 4144 AN XY: 74468

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0820

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0600

Alfa AF: 0.0409 Hom.: 100

Bravo AF: 0.0668

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs10495584; hg19: chr2-11959983;