rs145752858

Variant names:

• chr1-20116373-C-T
• rs145752858
• NM_012400.4:c.145G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-20116373-C-T
• chr1-20116373-C-A
• chr1-20116373-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.07
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012400.4. 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
	PLA2G2D	NM_012400.4	MANE Select	c.145G>A	p.Gly49Arg	missense	Exon 2 of 4	NP_036532.1	Q9UNK4-1
	PLA2G2D	NM_001271814.2		c.145G>A	p.Gly49Arg	missense	Exon 2 of 3	NP_001258743.1	Q9UNK4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2D	ENST00000375105.8	TSL:1 MANE Select	c.145G>A	p.Gly49Arg	missense	Exon 2 of 4	ENSP00000364246.3	Q9UNK4-1
	PLA2G2D	ENST00000617227.1	TSL:1	c.145G>A	p.Gly49Arg	missense	Exon 2 of 3	ENSP00000482871.1	Q9UNK4-2

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152206 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000135 AC: 34 AN: 251428 AF XY: 0.000103

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 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

African (AFR) AF: 0.00131 AC: 44 AN: 33478

American (AMR) AF: 0.000179 AC: 8 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111984

Other (OTH) AF: 0.000281 AC: 17 AN: 60396

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74490

African (AFR) AF: 0.000914 AC: 38 AN: 41584

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000165 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		3.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Uncertain	0.41
Sift	Benign	0.14	T
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.95		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
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

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