rs11570771

Variant names:

• chr22-38111572-G-C
• rs11570771
• NM_003560.4:c.*589C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-38111572-G-C
• chr22-38111572-G-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003560.4(PLA2G6):​c.*589C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 169,418 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (14 hom., cov: 33)
  • Exomes 𝑓: 0.010 (3 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0630
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-38111572-G-C is Benign according to our data. Variant chr22-38111572-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 341624.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00999 (1521/152292) while in subpopulation NFE AF = 0.0164 (1117/68014). AF 95% confidence interval is 0.0156. There are 14 homozygotes in GnomAd4. There are 735 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

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.*589C>G		3_prime_UTR	Exon 17 of 17	NP_003551.2
	PLA2G6	NM_001349864.2		c.*589C>G		3_prime_UTR	Exon 17 of 17	NP_001336793.1	O60733-1
	PLA2G6	NM_001004426.3		c.*589C>G		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.*589C>G		3_prime_UTR	Exon 17 of 17	ENSP00000333142.3	O60733-1
	PLA2G6	ENST00000402064.5	TSL:1	c.*589C>G		3_prime_UTR	Exon 16 of 16	ENSP00000386100.1	O60733-2
	PLA2G6	ENST00000663895.1		c.*589C>G		3_prime_UTR	Exon 17 of 17	ENSP00000499712.1	O60733-1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1521 AN: 152174 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.0104 AC: 178 AN: 17126 Hom.: 3 Cov.: 0 AF XY: 0.0104 AC XY: 91 AN XY: 8772

African (AFR) AF: 0.00 AC: 0 AN: 254

American (AMR) AF: 0.00373 AC: 11 AN: 2952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 208

East Asian (EAS) AF: 0.00 AC: 0 AN: 760

South Asian (SAS) AF: 0.00726 AC: 17 AN: 2342

European-Finnish (FIN) AF: 0.0101 AC: 4 AN: 398

Middle Eastern (MID) AF: 0.0263 AC: 1 AN: 38

European-Non Finnish (NFE) AF: 0.0147 AC: 138 AN: 9386

Other (OTH) AF: 0.00888 AC: 7 AN: 788

GnomAD4 genome AF: 0.00999 AC: 1521 AN: 152292 Hom.: 14 Cov.: 33 AF XY: 0.00987 AC XY: 735 AN XY: 74466

African (AFR) AF: 0.00284 AC: 118 AN: 41566

American (AMR) AF: 0.00555 AC: 85 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4820

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1117 AN: 68014

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.0138 Hom.: 3

Bravo AF: 0.00894

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	PLA2G6-associated neurodegeneration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism

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: rs11570771; hg19: chr22-38507579;