rs3890451

Variant names:

• chr22-38199813-T-G
• rs3890451
• ENST00000660610.1:c.-42+14640A>C

Variant summary

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

The ENST00000660610.1(PLA2G6):​c.-42+14640A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 141,868 control chromosomes in the GnomAD database, including 20,867 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 0.54 (20867 hom., cov: 24)
• Consequence: PLA2G6 ENST00000660610.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 0 publications found

Genes affected

PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

PLA2G6 Gene-Disease associations (from GenCC):

• neurodegeneration with brain iron accumulation 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• neurodegeneration with brain iron accumulation 2B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• PLA2G6-associated neurodegeneration

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive Parkinson disease 14

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ENSG00000298301 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000660610.1	c.-42+14640A>C		intron_variant	Intron 1 of 16			ENSP00000499555.1
PLA2G6	ENST00000594306.1	c.-46+5480A>C		intron_variant	Intron 1 of 1	4		ENSP00000473160.1
ENSG00000298301	ENST00000754572.1	n.184+3473A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 76165 AN: 141832 Hom.: 20888 Cov.: 24

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.507

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.560

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 76154 AN: 141868 Hom.: 20867 Cov.: 24 AF XY: 0.533 AC XY: 36429 AN XY: 68314

African (AFR) AF: 0.376 AC: 14061 AN: 37396

American (AMR) AF: 0.518 AC: 7233 AN: 13950

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2065 AN: 3422

East Asian (EAS) AF: 0.743 AC: 3585 AN: 4826

South Asian (SAS) AF: 0.475 AC: 2157 AN: 4542

European-Finnish (FIN) AF: 0.612 AC: 5079 AN: 8298

Middle Eastern (MID) AF: 0.504 AC: 130 AN: 258

European-Non Finnish (NFE) AF: 0.609 AC: 40370 AN: 66308

Other (OTH) AF: 0.557 AC: 1106 AN: 1986

Alfa AF: 0.479 Hom.: 3889

Bravo AF: 0.519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.14
PhyloP100		-0.90

Splicing

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

Other links and lift over

dbSNP: rs3890451; hg19: chr22-38595820;