1-19975434-A-T

Variant names:

• chr1-19975434-A-T
• rs876018
• ENST00000400520.8:c.*267T>A

Variant summary

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

The NM_001161729.1(PLA2G2A):​c.*267T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 508,038 control chromosomes in the GnomAD database, including 7,168 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 0.18 (2693 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4475 hom.)
• Consequence: PLA2G2A NM_001161729.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161729.1. 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_001161729.1		c.*267T>A		3_prime_UTR	Exon 5 of 5	NP_001155201.1	P14555
	PLA2G2A	NM_001395463.1	MANE Select	c.*267T>A		downstream_gene	N/A	NP_001382392.1	P14555
	PLA2G2A	NM_000300.4		c.*267T>A		downstream_gene	N/A	NP_000291.1	P14555

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2A	ENST00000400520.8	TSL:1	c.*267T>A		3_prime_UTR	Exon 5 of 5	ENSP00000383364.3	P14555
	PLA2G2A	ENST00000907286.1		c.*267T>A		splice_region	Exon 4 of 4	ENSP00000577345.1
	PLA2G2A	ENST00000932016.1		c.*267T>A		splice_region	Exon 5 of 5	ENSP00000602075.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27785 AN: 152012 Hom.: 2686 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.154 AC: 54645 AN: 355908 Hom.: 4475 Cov.: 0 AF XY: 0.150 AC XY: 28348 AN XY: 188422

African (AFR) AF: 0.252 AC: 2582 AN: 10266

American (AMR) AF: 0.205 AC: 3243 AN: 15800

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 2182 AN: 10760

East Asian (EAS) AF: 0.118 AC: 2701 AN: 22894

South Asian (SAS) AF: 0.128 AC: 5617 AN: 43980

European-Finnish (FIN) AF: 0.111 AC: 2288 AN: 20704

Middle Eastern (MID) AF: 0.176 AC: 270 AN: 1536

European-Non Finnish (NFE) AF: 0.154 AC: 32373 AN: 209636

Other (OTH) AF: 0.167 AC: 3389 AN: 20332

GnomAD4 genome AF: 0.183 AC: 27842 AN: 152130 Hom.: 2693 Cov.: 32 AF XY: 0.183 AC XY: 13579 AN XY: 74378

African (AFR) AF: 0.241 AC: 9983 AN: 41470

American (AMR) AF: 0.214 AC: 3275 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3468

East Asian (EAS) AF: 0.121 AC: 623 AN: 5168

South Asian (SAS) AF: 0.121 AC: 584 AN: 4822

European-Finnish (FIN) AF: 0.108 AC: 1147 AN: 10598

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10948 AN: 67998

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.0807 Hom.: 104

Bravo AF: 0.194

Asia WGS AF: 0.136 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.80
PhyloP100		-0.39
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: rs876018; hg19: chr1-20301927;