1-20116373-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_012400.4(PLA2G2D):​c.145G>A​(p.Gly49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,614,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

PLA2G2D
NM_012400.4 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07
Variant links:
Genes affected
PLA2G2D (HGNC:9033): (phospholipase A2 group IID) This gene encodes a secreted member of the phospholipase A2 family, and is found in a cluster of related family members on chromosome 1. Phospholipase A2 family members hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce lysophospholipids and free fatty acid. This gene may be involved in inflammation and immune response, and in weight loss associated with chronic obstructive pulmonary disease. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity PA2GD_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLA2G2DNM_012400.4 linkuse as main transcriptc.145G>A p.Gly49Arg missense_variant 2/4 ENST00000375105.8
PLA2G2DNM_001271814.2 linkuse as main transcriptc.145G>A p.Gly49Arg missense_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLA2G2DENST00000375105.8 linkuse as main transcriptc.145G>A p.Gly49Arg missense_variant 2/41 NM_012400.4 P1Q9UNK4-1
PLA2G2DENST00000617227.1 linkuse as main transcriptc.145G>A p.Gly49Arg missense_variant 2/31 Q9UNK4-2

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000917
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000135
AC:
34
AN:
251428
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00105
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000791
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000965
AC:
141
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.0000853
AC XY:
62
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00131
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000277
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000486
Gnomad4 OTH exome
AF:
0.000281
GnomAD4 genome
AF:
0.000341
AC:
52
AN:
152326
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000914
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000111
Hom.:
0
Bravo
AF:
0.000521
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2023The c.145G>A (p.G49R) alteration is located in exon 2 (coding exon 2) of the PLA2G2D gene. This alteration results from a G to A substitution at nucleotide position 145, causing the glycine (G) at amino acid position 49 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Uncertain
0.080
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.50
T;T
MetaSVM
Benign
-0.46
T
MutationAssessor
Pathogenic
3.2
M;.
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.53
T
PROVEAN
Pathogenic
-7.5
D;.
REVEL
Uncertain
0.41
Sift
Benign
0.14
T;.
Sift4G
Uncertain
0.039
D;D
Polyphen
1.0
D;.
Vest4
0.61
MutPred
0.95
Gain of methylation at G49 (P = 0.0153);Gain of methylation at G49 (P = 0.0153);
MVP
0.61
MPC
0.26
ClinPred
0.57
D
GERP RS
5.3
Varity_R
0.63
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.31
Position offset: -40

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145752858; hg19: chr1-20442866; COSMIC: COSV105318720; API