NM_003560.4:c.*183_*187delCCGCC

Variant names:

• chr22-38111973-AGGCGG-A
• rs139718702
• NM_003560.4:c.*183_*187delCCGCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003560.4(PLA2G6):​c.*183_*187delCCGCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 651,406 control chromosomes in the GnomAD database, including 2,586 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (428 hom., cov: 31)
  • Exomes 𝑓: 0.084 (2158 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.292
• Publications: 4 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• 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: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 22-38111973-AGGCGG-A is Benign according to our data. Variant chr22-38111973-AGGCGG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 341632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003560.4. 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
	PLA2G6	NM_003560.4	MANE Select	c.*183_*187delCCGCC		3_prime_UTR	Exon 17 of 17	NP_003551.2
	PLA2G6	NM_001349864.2		c.*183_*187delCCGCC		3_prime_UTR	Exon 17 of 17	NP_001336793.1	O60733-1
	PLA2G6	NM_001004426.3		c.*183_*187delCCGCC		3_prime_UTR	Exon 16 of 16	NP_001004426.1	O60733-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	ENST00000332509.8	TSL:1 MANE Select	c.*183_*187delCCGCC		3_prime_UTR	Exon 17 of 17	ENSP00000333142.3	O60733-1
	PLA2G6	ENST00000402064.5	TSL:1	c.*183_*187delCCGCC		3_prime_UTR	Exon 16 of 16	ENSP00000386100.1	O60733-2
	PLA2G6	ENST00000668949.1		c.*183_*187delCCGCC		3_prime_UTR	Exon 17 of 17	ENSP00000499711.1	A0A590UK51

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10034 AN: 152124 Hom.: 427 Cov.: 31

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0779

GnomAD4 exome AF: 0.0836 AC: 41750 AN: 499164 Hom.: 2158 AF XY: 0.0833 AC XY: 22027 AN XY: 264408

African (AFR) AF: 0.0297 AC: 413 AN: 13894

American (AMR) AF: 0.0517 AC: 1298 AN: 25122

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 1954 AN: 15358

East Asian (EAS) AF: 0.215 AC: 6751 AN: 31366

South Asian (SAS) AF: 0.0762 AC: 3869 AN: 50788

European-Finnish (FIN) AF: 0.118 AC: 3721 AN: 31474

Middle Eastern (MID) AF: 0.0774 AC: 165 AN: 2132

European-Non Finnish (NFE) AF: 0.0707 AC: 21296 AN: 301106

Other (OTH) AF: 0.0818 AC: 2283 AN: 27924

GnomAD4 genome AF: 0.0659 AC: 10039 AN: 152242 Hom.: 428 Cov.: 31 AF XY: 0.0688 AC XY: 5119 AN XY: 74434

African (AFR) AF: 0.0273 AC: 1134 AN: 41554

American (AMR) AF: 0.0489 AC: 749 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5168

South Asian (SAS) AF: 0.0847 AC: 409 AN: 4830

European-Finnish (FIN) AF: 0.115 AC: 1222 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4774 AN: 67992

Other (OTH) AF: 0.0776 AC: 164 AN: 2114

Alfa AF: 0.0688 Hom.: 59

Bravo AF: 0.0587

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Infantile neuroaxonal dystrophy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs139718702; hg19: chr22-38507980; COSMIC: COSV59268402; COSMIC: COSV59268402;