18-2921779-T-C

Variant names:

• chr18-2921779-T-C
• rs2282636
• NM_001375808.2:c.2328-132A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375808.2(LPIN2):​c.2328-132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 793,214 control chromosomes in the GnomAD database, including 42,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7837 hom., cov: 33)
  • Exomes 𝑓: 0.32 (34672 hom.)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.308
• Publications: 10 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

ENSG00000272625 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-2921779-T-C is Benign according to our data. Variant chr18-2921779-T-C is described in ClinVar as Benign. ClinVar VariationId is 1180093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

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.2328-132A>G		intron	N/A	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.2328-132A>G		intron	N/A	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.2328-132A>G		intron	N/A	NP_055461.1	Q92539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.2328-132A>G		intron	N/A	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.2328-132A>G		intron	N/A	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.2328-132A>G		intron	N/A	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47229 AN: 152090 Hom.: 7817 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.314

GnomAD4 exome AF: 0.316 AC: 202528 AN: 641006 Hom.: 34672 AF XY: 0.320 AC XY: 108793 AN XY: 340058

African (AFR) AF: 0.313 AC: 5171 AN: 16534

American (AMR) AF: 0.393 AC: 12531 AN: 31908

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 4541 AN: 19596

East Asian (EAS) AF: 0.619 AC: 20053 AN: 32422

South Asian (SAS) AF: 0.417 AC: 25476 AN: 61106

European-Finnish (FIN) AF: 0.284 AC: 10393 AN: 36592

Middle Eastern (MID) AF: 0.287 AC: 767 AN: 2670

European-Non Finnish (NFE) AF: 0.278 AC: 113045 AN: 407220

Other (OTH) AF: 0.320 AC: 10551 AN: 32958

GnomAD4 genome AF: 0.311 AC: 47290 AN: 152208 Hom.: 7837 Cov.: 33 AF XY: 0.315 AC XY: 23467 AN XY: 74422

African (AFR) AF: 0.310 AC: 12894 AN: 41528

American (AMR) AF: 0.362 AC: 5537 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3468

East Asian (EAS) AF: 0.638 AC: 3299 AN: 5170

South Asian (SAS) AF: 0.438 AC: 2115 AN: 4834

European-Finnish (FIN) AF: 0.275 AC: 2917 AN: 10612

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18694 AN: 67992

Other (OTH) AF: 0.318 AC: 673 AN: 2116

Alfa AF: 0.288 Hom.: 3679

Bravo AF: 0.315

Asia WGS AF: 0.543 AC: 1885 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.44
DANN	Benign	0.40
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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: rs2282636; hg19: chr18-2921777;