rs140687415

Variant names:

• chr22-38112013-G-A
• rs140687415
• NM_003560.4:c.*148C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38112013-G-A
• chr22-38112013-G-C

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.*148C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000832 in 892,706 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.135
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 22-38112013-G-A is Benign according to our data. Variant chr22-38112013-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1219137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00307 (467/152336) while in subpopulation AFR AF = 0.0105 (435/41580). AF 95% confidence interval is 0.00965. There are 2 homozygotes in GnomAd4. There are 223 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.*148C>T		3_prime_UTR	Exon 17 of 17	NP_003551.2
	PLA2G6	NM_001349864.2		c.*148C>T		3_prime_UTR	Exon 17 of 17	NP_001336793.1	O60733-1
	PLA2G6	NM_001004426.3		c.*148C>T		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.*148C>T		3_prime_UTR	Exon 17 of 17	ENSP00000333142.3	O60733-1
	PLA2G6	ENST00000402064.5	TSL:1	c.*148C>T		3_prime_UTR	Exon 16 of 16	ENSP00000386100.1	O60733-2
	PLA2G6	ENST00000668949.1		c.*148C>T		3_prime_UTR	Exon 17 of 17	ENSP00000499711.1	A0A590UK51

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 466 AN: 152218 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.000373 AC: 276 AN: 740370 Hom.: 1 Cov.: 10 AF XY: 0.000325 AC XY: 125 AN XY: 384844

African (AFR) AF: 0.00910 AC: 174 AN: 19114

American (AMR) AF: 0.00101 AC: 33 AN: 32780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19738

East Asian (EAS) AF: 0.0000922 AC: 3 AN: 32554

South Asian (SAS) AF: 0.000267 AC: 17 AN: 63586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38920

Middle Eastern (MID) AF: 0.000364 AC: 1 AN: 2748

European-Non Finnish (NFE) AF: 0.0000364 AC: 18 AN: 494910

Other (OTH) AF: 0.000833 AC: 30 AN: 36020

GnomAD4 genome AF: 0.00307 AC: 467 AN: 152336 Hom.: 2 Cov.: 33 AF XY: 0.00299 AC XY: 223 AN XY: 74488

African (AFR) AF: 0.0105 AC: 435 AN: 41580

American (AMR) AF: 0.00157 AC: 24 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00340

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.77
PhyloP100		-0.14

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: rs140687415; hg19: chr22-38508020;