22-38111811-G-T

Variant names:

• chr22-38111811-G-T
• rs11570770
• NM_003560.4:c.*350C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003560.4(PLA2G6):​c.*350C>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 0.0982 in 369,066 control chromosomes in the GnomAD database, including 1,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (800 hom., cov: 33)
  • Exomes 𝑓: 0.099 (1194 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.82
• Publications: 3 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: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• neurodegeneration with brain iron accumulation 2B

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

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

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-38111811-G-T is Benign according to our data. Variant chr22-38111811-G-T is described in ClinVar as Benign. ClinVar VariationId is 341629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 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.*350C>A		3_prime_UTR	Exon 17 of 17	NP_003551.2
	PLA2G6	NM_001349864.2		c.*350C>A		3_prime_UTR	Exon 17 of 17	NP_001336793.1	O60733-1
	PLA2G6	NM_001004426.3		c.*350C>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.*350C>A		3_prime_UTR	Exon 17 of 17	ENSP00000333142.3	O60733-1
	PLA2G6	ENST00000402064.5	TSL:1	c.*350C>A		3_prime_UTR	Exon 16 of 16	ENSP00000386100.1	O60733-2
	PLA2G6	ENST00000660610.1		c.*350C>A		3_prime_UTR	Exon 17 of 17	ENSP00000499555.1	O60733-1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14738 AN: 152068 Hom.: 798 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0992 AC: 21513 AN: 216880 Hom.: 1194 Cov.: 0 AF XY: 0.103 AC XY: 12138 AN XY: 117306

African (AFR) AF: 0.117 AC: 706 AN: 6030

American (AMR) AF: 0.0589 AC: 648 AN: 11000

Ashkenazi Jewish (ASJ) AF: 0.0901 AC: 494 AN: 5484

East Asian (EAS) AF: 0.139 AC: 1366 AN: 9822

South Asian (SAS) AF: 0.140 AC: 5621 AN: 40240

European-Finnish (FIN) AF: 0.0554 AC: 545 AN: 9834

Middle Eastern (MID) AF: 0.129 AC: 104 AN: 804

European-Non Finnish (NFE) AF: 0.0895 AC: 10987 AN: 122710

Other (OTH) AF: 0.0951 AC: 1042 AN: 10956

GnomAD4 genome AF: 0.0969 AC: 14742 AN: 152186 Hom.: 800 Cov.: 33 AF XY: 0.0946 AC XY: 7035 AN XY: 74398

African (AFR) AF: 0.119 AC: 4942 AN: 41510

American (AMR) AF: 0.0737 AC: 1127 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3470

East Asian (EAS) AF: 0.148 AC: 768 AN: 5172

South Asian (SAS) AF: 0.142 AC: 686 AN: 4820

European-Finnish (FIN) AF: 0.0515 AC: 547 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5955 AN: 67984

Other (OTH) AF: 0.105 AC: 221 AN: 2110

Alfa AF: 0.0263 Hom.: 12

Bravo AF: 0.0999

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	PLA2G6-associated neurodegeneration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.54
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs11570770; hg19: chr22-38507818; COSMIC: COSV59273871; COSMIC: COSV59273871;