1-19978469-C-T

Variant names:

• chr1-19978469-C-T
• rs2236771
• NM_001395463.1:c.96G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001395463.1(PLA2G2A):​c.96G>A​(p.Thr32Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T32T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: PLA2G2A NM_001395463.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 22 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 33 AD gene.

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.96G>A	p.Thr32Thr	synonymous	Exon 3 of 5	NP_001382392.1	P14555
	PLA2G2A	NM_000300.4		c.96G>A	p.Thr32Thr	synonymous	Exon 4 of 6	NP_000291.1	P14555
	PLA2G2A	NM_001161727.2		c.96G>A	p.Thr32Thr	synonymous	Exon 4 of 6	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.96G>A	p.Thr32Thr	synonymous	Exon 3 of 5	ENSP00000504762.1	P14555
	PLA2G2A	ENST00000375111.7	TSL:1	c.96G>A	p.Thr32Thr	synonymous	Exon 4 of 6	ENSP00000364252.3	P14555
	PLA2G2A	ENST00000400520.8	TSL:1	c.96G>A	p.Thr32Thr	synonymous	Exon 3 of 5	ENSP00000383364.3	P14555

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251184 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461570 Hom.: 0 Cov.: 36 AF XY: 0.0000261 AC XY: 19 AN XY: 727100

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.9
DANN	Benign	0.55
PhyloP100		-2.0
Mutation Taster		=100/0	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: rs2236771; hg19: chr1-20304962;