rs10902224

Variant names:

• chr11-822588-C-T
• rs10902224
• NM_020376.4:c.678C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-822588-C-T
• chr11-822588-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020376.4(PNPLA2):​c.678C>T​(p.Leu226Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,613,588 control chromosomes in the GnomAD database, including 2,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (252 hom., cov: 33)
  • Exomes 𝑓: 0.022 (2042 hom.)
• Consequence: PNPLA2 NM_020376.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0430
• Publications: 10 publications found

Genes affected

PNPLA2 (HGNC:30802): (patatin like phospholipase domain containing 2) This gene encodes an enzyme which catalyzes the first step in the hydrolysis of triglycerides in adipose tissue. Mutations in this gene are associated with neutral lipid storage disease with myopathy. [provided by RefSeq, Jul 2010]

PNPLA2 Gene-Disease associations (from GenCC):

• neutral lipid storage myopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 11-822588-C-T is Benign according to our data. Variant chr11-822588-C-T is described in ClinVar as Benign. ClinVar VariationId is 261243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.043 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020376.4. 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
	PNPLA2	NM_020376.4	MANE Select	c.678C>T	p.Leu226Leu	synonymous	Exon 5 of 10	NP_065109.1	Q96AD5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNPLA2	ENST00000336615.9	TSL:1 MANE Select	c.678C>T	p.Leu226Leu	synonymous	Exon 5 of 10	ENSP00000337701.4	Q96AD5-1
	PNPLA2	ENST00000869283.1		c.1062C>T	p.Leu354Leu	synonymous	Exon 6 of 11	ENSP00000539342.1
	PNPLA2	ENST00000869284.1		c.678C>T	p.Leu226Leu	synonymous	Exon 5 of 10	ENSP00000539343.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4941 AN: 152226 Hom.: 252 Cov.: 33

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0207

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00729

Gnomad OTH AF: 0.0272

GnomAD2 exomes AF: 0.0432 AC: 10849 AN: 251198 AF XY: 0.0454

Gnomad AFR exome AF: 0.0444

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.0250

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.00214

Gnomad NFE exome AF: 0.00712

Gnomad OTH exome AF: 0.0295

GnomAD4 exome AF: 0.0220 AC: 32154 AN: 1461244 Hom.: 2042 Cov.: 32 AF XY: 0.0246 AC XY: 17915 AN XY: 726966

African (AFR) AF: 0.0457 AC: 1528 AN: 33468

American (AMR) AF: 0.0144 AC: 646 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 591 AN: 26134

East Asian (EAS) AF: 0.229 AC: 9101 AN: 39696

South Asian (SAS) AF: 0.120 AC: 10340 AN: 86244

European-Finnish (FIN) AF: 0.00234 AC: 124 AN: 53018

Middle Eastern (MID) AF: 0.0146 AC: 84 AN: 5764

European-Non Finnish (NFE) AF: 0.00687 AC: 7641 AN: 1111834

Other (OTH) AF: 0.0348 AC: 2099 AN: 60364

GnomAD4 genome AF: 0.0326 AC: 4960 AN: 152344 Hom.: 252 Cov.: 33 AF XY: 0.0357 AC XY: 2658 AN XY: 74502

African (AFR) AF: 0.0451 AC: 1876 AN: 41574

American (AMR) AF: 0.0355 AC: 544 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 72 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1243 AN: 5182

South Asian (SAS) AF: 0.131 AC: 632 AN: 4832

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00729 AC: 496 AN: 68032

Other (OTH) AF: 0.0284 AC: 60 AN: 2114

Alfa AF: 0.0150 Hom.: 26

Bravo AF: 0.0323

Asia WGS AF: 0.165 AC: 574 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.00771

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Neutral lipid storage myopathy (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.4
DANN	Benign	0.75
PhyloP100		-0.043
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: rs10902224; hg19: chr11-822588; COSMIC: COSV60744149; COSMIC: COSV60744149;