22-38111970-G-T

Variant names:

• chr22-38111970-G-T
• rs886057499
• NM_003560.4:c.*191C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003560.4(PLA2G6):​c.*191C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 494,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• 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, 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.*191C>A		3_prime_UTR	Exon 17 of 17	NP_003551.2
	PLA2G6	NM_001349864.2		c.*191C>A		3_prime_UTR	Exon 17 of 17	NP_001336793.1	O60733-1
	PLA2G6	NM_001004426.3		c.*191C>A		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.*191C>A		3_prime_UTR	Exon 17 of 17	ENSP00000333142.3	O60733-1
	PLA2G6	ENST00000402064.5	TSL:1	c.*191C>A		3_prime_UTR	Exon 16 of 16	ENSP00000386100.1	O60733-2
	PLA2G6	ENST00000668949.1		c.*191C>A		3_prime_UTR	Exon 17 of 17	ENSP00000499711.1	A0A590UK51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000121 AC: 6 AN: 494466 Hom.: 0 Cov.: 5 AF XY: 0.0000115 AC XY: 3 AN XY: 261818

African (AFR) AF: 0.00 AC: 0 AN: 13842

American (AMR) AF: 0.00 AC: 0 AN: 24798

Ashkenazi Jewish (ASJ) AF: 0.0000661 AC: 1 AN: 15120

East Asian (EAS) AF: 0.00 AC: 0 AN: 31318

South Asian (SAS) AF: 0.00 AC: 0 AN: 50378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31040

Middle Eastern (MID) AF: 0.000475 AC: 1 AN: 2106

European-Non Finnish (NFE) AF: 0.0000134 AC: 4 AN: 298156

Other (OTH) AF: 0.00 AC: 0 AN: 27708

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.93
DANN	Benign	0.87
PhyloP100		0.52

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: rs886057499; hg19: chr22-38507977;