1-19978292-C-T

Variant names:

• chr1-19978292-C-T
• rs2236772
• NM_001395463.1:c.185+88G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395463.1(PLA2G2A):​c.185+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,498,284 control chromosomes in the GnomAD database, including 1,426 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (130 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1296 hom.)
• Consequence: PLA2G2A NM_001395463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 6 publications found

Genes affected

PLA2G2A (HGNC:9031): (phospholipase A2 group IIA) The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5' UTRs have been found for this gene.[provided by RefSeq, Sep 2009]

PLA2G2A Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395463.1. 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
	PLA2G2A	NM_001395463.1	MANE Select	c.185+88G>A		intron	N/A	NP_001382392.1	P14555
	PLA2G2A	NM_000300.4		c.185+88G>A		intron	N/A	NP_000291.1	P14555
	PLA2G2A	NM_001161727.2		c.185+88G>A		intron	N/A	NP_001155199.1	P14555

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2A	ENST00000482011.3	TSL:1 MANE Select	c.185+88G>A		intron	N/A	ENSP00000504762.1	P14555
	PLA2G2A	ENST00000375111.7	TSL:1	c.185+88G>A		intron	N/A	ENSP00000364252.3	P14555
	PLA2G2A	ENST00000400520.8	TSL:1	c.185+88G>A		intron	N/A	ENSP00000383364.3	P14555

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4935 AN: 152128 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.0632

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0353 AC: 47496 AN: 1346038 Hom.: 1296 Cov.: 20 AF XY: 0.0360 AC XY: 24214 AN XY: 673118

African (AFR) AF: 0.00591 AC: 184 AN: 31122

American (AMR) AF: 0.104 AC: 4447 AN: 42636

Ashkenazi Jewish (ASJ) AF: 0.0828 AC: 2064 AN: 24934

East Asian (EAS) AF: 0.105 AC: 4079 AN: 38794

South Asian (SAS) AF: 0.0664 AC: 5486 AN: 82636

European-Finnish (FIN) AF: 0.0286 AC: 1415 AN: 49404

Middle Eastern (MID) AF: 0.0412 AC: 169 AN: 4098

European-Non Finnish (NFE) AF: 0.0270 AC: 27451 AN: 1016026

Other (OTH) AF: 0.0390 AC: 2201 AN: 56388

GnomAD4 genome AF: 0.0324 AC: 4931 AN: 152246 Hom.: 130 Cov.: 33 AF XY: 0.0350 AC XY: 2609 AN XY: 74444

African (AFR) AF: 0.00748 AC: 311 AN: 41556

American (AMR) AF: 0.0799 AC: 1223 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 290 AN: 3464

East Asian (EAS) AF: 0.0982 AC: 507 AN: 5164

South Asian (SAS) AF: 0.0635 AC: 306 AN: 4820

European-Finnish (FIN) AF: 0.0269 AC: 285 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0284 AC: 1933 AN: 68010

Other (OTH) AF: 0.0237 AC: 50 AN: 2114

Alfa AF: 0.0337 Hom.: 245

Bravo AF: 0.0353

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		-0.38
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: rs2236772; hg19: chr1-20304785;