rs17886056

Variant names:

• chr18-2960694-G-A
• rs17886056
• NM_001375808.2:c.147C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001375808.2(LPIN2):​c.147C>T​(p.His49His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,958 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (14 hom., cov: 31)
  • Exomes 𝑓: 0.00065 (10 hom.)
• Consequence: LPIN2 NM_001375808.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0150
• Publications: 1 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

LPIN2-AS1 (HGNC:58311):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 18-2960694-G-A is Benign according to our data. Variant chr18-2960694-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.015 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00654 (995/152074) while in subpopulation AFR AF = 0.0224 (930/41476). AF 95% confidence interval is 0.0212. There are 14 homozygotes in GnomAd4. There are 482 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.147C>T	p.His49His	synonymous	Exon 2 of 20	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.147C>T	p.His49His	synonymous	Exon 2 of 20	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.147C>T	p.His49His	synonymous	Exon 2 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.147C>T	p.His49His	synonymous	Exon 2 of 20	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.147C>T	p.His49His	synonymous	Exon 3 of 21	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.147C>T	p.His49His	synonymous	Exon 2 of 20	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.00654 AC: 994 AN: 151956 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00175 AC: 441 AN: 251386 AF XY: 0.00121

Gnomad AFR exome AF: 0.0235

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000646 AC: 944 AN: 1461884 Hom.: 10 Cov.: 32 AF XY: 0.000523 AC XY: 380 AN XY: 727244

African (AFR) AF: 0.0227 AC: 759 AN: 33480

American (AMR) AF: 0.00165 AC: 74 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1112006

Other (OTH) AF: 0.00151 AC: 91 AN: 60396

GnomAD4 genome AF: 0.00654 AC: 995 AN: 152074 Hom.: 14 Cov.: 31 AF XY: 0.00648 AC XY: 482 AN XY: 74336

African (AFR) AF: 0.0224 AC: 930 AN: 41476

American (AMR) AF: 0.00301 AC: 46 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67986

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00488 Hom.: 2

Bravo AF: 0.00727

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Majeed syndrome (3)
-	-	2	not specified (2)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.89
PhyloP100		-0.015
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	polymorphism

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: rs17886056; hg19: chr18-2960692;