chr18-2917154-T-C

Variant names:

• chr18-2917154-T-C
• rs1164
• NM_001375808.2:c.*3139A>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.*3139A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,242 control chromosomes in the GnomAD database, including 2,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2824 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPIN2 NM_001375808.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.384
• Publications: 13 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 18-2917154-T-C is Benign according to our data. Variant chr18-2917154-T-C is described in ClinVar as Benign. ClinVar VariationId is 326543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 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.*3139A>G		3_prime_UTR	Exon 20 of 20	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.*3139A>G		3_prime_UTR	Exon 20 of 20	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.*3139A>G		3_prime_UTR	Exon 20 of 20	NP_055461.1	Q92539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.*3139A>G		3_prime_UTR	Exon 20 of 20	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.*3139A>G		3_prime_UTR	Exon 21 of 21	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.*3139A>G		3_prime_UTR	Exon 20 of 20	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28147 AN: 152124 Hom.: 2824 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.194

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.185 AC: 28148 AN: 152242 Hom.: 2824 Cov.: 33 AF XY: 0.184 AC XY: 13704 AN XY: 74452

African (AFR) AF: 0.130 AC: 5398 AN: 41542

American (AMR) AF: 0.290 AC: 4436 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3470

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5186

South Asian (SAS) AF: 0.119 AC: 574 AN: 4834

European-Finnish (FIN) AF: 0.198 AC: 2098 AN: 10598

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14170 AN: 67998

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.208 Hom.: 6840

Bravo AF: 0.193

Asia WGS AF: 0.0680 AC: 236 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Majeed syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1164; hg19: chr18-2917152;