rs2236771

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-19978469-C-G
• chr1-19978469-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001395463.1(PLA2G2A):​c.96G>C​(p.Thr32Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,613,622 control chromosomes in the GnomAD database, including 8,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.078 (646 hom., cov: 32)
  • Exomes 𝑓: 0.094 (7492 hom.)
• Consequence: PLA2G2A NM_001395463.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-19978469-C-G is Benign according to our data. Variant chr1-19978469-C-G is described in ClinVar as Benign. ClinVar VariationId is 3059119.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.96G>C	p.Thr32Thr	synonymous_variant	Exon 3 of 5	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.96G>C	p.Thr32Thr	synonymous_variant	Exon 3 of 5	1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11828 AN: 152076 Hom.: 650 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0690

GnomAD2 exomes AF: 0.109 AC: 27504 AN: 251184 AF XY: 0.109

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.0966

Gnomad NFE exome AF: 0.0881

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0943 AC: 137803 AN: 1461428 Hom.: 7492 Cov.: 36 AF XY: 0.0947 AC XY: 68840 AN XY: 727022

African (AFR) AF: 0.0140 AC: 470 AN: 33480

American (AMR) AF: 0.156 AC: 6985 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2933 AN: 26128

East Asian (EAS) AF: 0.238 AC: 9463 AN: 39694

South Asian (SAS) AF: 0.122 AC: 10562 AN: 86232

European-Finnish (FIN) AF: 0.0932 AC: 4959 AN: 53188

Middle Eastern (MID) AF: 0.131 AC: 747 AN: 5696

European-Non Finnish (NFE) AF: 0.0863 AC: 95923 AN: 1111916

Other (OTH) AF: 0.0954 AC: 5761 AN: 60380

GnomAD4 genome AF: 0.0776 AC: 11817 AN: 152194 Hom.: 646 Cov.: 32 AF XY: 0.0818 AC XY: 6083 AN XY: 74382

African (AFR) AF: 0.0169 AC: 703 AN: 41556

American (AMR) AF: 0.122 AC: 1872 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3466

East Asian (EAS) AF: 0.226 AC: 1165 AN: 5148

South Asian (SAS) AF: 0.127 AC: 611 AN: 4816

European-Finnish (FIN) AF: 0.0973 AC: 1031 AN: 10600

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0854 AC: 5807 AN: 67998

Other (OTH) AF: 0.0669 AC: 141 AN: 2108

Alfa AF: 0.0827 Hom.: 153

Bravo AF: 0.0788

Asia WGS AF: 0.149 AC: 518 AN: 3476

EpiCase AF: 0.0839

EpiControl AF: 0.0887

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PLA2G2A-related disorder Benign:1

Nov 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.83
DANN	Benign	0.40
PhyloP100		-2.0
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: rs2236771; hg19: chr1-20304962; COSMIC: COSV64287129;