rs17555442

Variant names:

• chr18-2922151-G-A
• rs17555442
• NM_001375808.2:c.2223C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2922151-G-A
• chr18-2922151-G-C
• chr18-2922151-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001375808.2(LPIN2):​c.2223C>T​(p.Ala741Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,974 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (13 hom., cov: 33)
  • Exomes 𝑓: 0.014 (211 hom.)
• Consequence: LPIN2 NM_001375808.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7 O:1
• Conservation: PhyloP100: -1.37
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 18-2922151-G-A is Benign according to our data. Variant chr18-2922151-G-A is described in ClinVar as Benign. ClinVar VariationId is 97815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1737/152282) while in subpopulation NFE AF = 0.0151 (1026/68008). AF 95% confidence interval is 0.0143. There are 13 homozygotes in GnomAd4. There are 790 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 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.2223C>T	p.Ala741Ala	synonymous	Exon 17 of 20	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.2223C>T	p.Ala741Ala	synonymous	Exon 17 of 20	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.2223C>T	p.Ala741Ala	synonymous	Exon 17 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.2223C>T	p.Ala741Ala	synonymous	Exon 17 of 20	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.2223C>T	p.Ala741Ala	synonymous	Exon 18 of 21	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.2223C>T	p.Ala741Ala	synonymous	Exon 17 of 20	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1738 AN: 152164 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00762

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.0114 AC: 2850 AN: 250898 AF XY: 0.0117

Gnomad AFR exome AF: 0.00702

Gnomad AMR exome AF: 0.00850

Gnomad ASJ exome AF: 0.0409

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00342

Gnomad NFE exome AF: 0.0157

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0141 AC: 20539 AN: 1461692 Hom.: 211 Cov.: 33 AF XY: 0.0139 AC XY: 10083 AN XY: 727164

African (AFR) AF: 0.00783 AC: 262 AN: 33480

American (AMR) AF: 0.00890 AC: 398 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0419 AC: 1095 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00261 AC: 225 AN: 86258

European-Finnish (FIN) AF: 0.00389 AC: 207 AN: 53226

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5768

European-Non Finnish (NFE) AF: 0.0156 AC: 17301 AN: 1112006

Other (OTH) AF: 0.0147 AC: 885 AN: 60394

GnomAD4 genome AF: 0.0114 AC: 1737 AN: 152282 Hom.: 13 Cov.: 33 AF XY: 0.0106 AC XY: 790 AN XY: 74472

African (AFR) AF: 0.00758 AC: 315 AN: 41566

American (AMR) AF: 0.00889 AC: 136 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00472 AC: 50 AN: 10596

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1026 AN: 68008

Other (OTH) AF: 0.0147 AC: 31 AN: 2112

Alfa AF: 0.0143 Hom.: 26

Bravo AF: 0.0124

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.0171

EpiControl AF: 0.0190

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Majeed syndrome (4)
-	-	2	not provided (2)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.62
DANN	Benign	0.73
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=95/5	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: rs17555442; hg19: chr18-2922149;