rs112920700

Variant names:

• chr22-38112080-C-A
• rs112920700
• NM_003560.4:c.*81G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38112080-C-A
• chr22-38112080-C-G

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.*81G>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 0.00061 in 1,501,892 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 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.477
• 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=-0.76).
• BP6: Variant 22-38112080-C-A is Benign according to our data. Variant chr22-38112080-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1196934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00322 (490/152226) while in subpopulation AFR AF = 0.011 (457/41552). AF 95% confidence interval is 0.0102. There are 3 homozygotes in GnomAd4. There are 239 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.*81G>T		3_prime_UTR	Exon 17 of 17	NP_003551.2
	PLA2G6	NM_001349864.2		c.*81G>T		3_prime_UTR	Exon 17 of 17	NP_001336793.1	O60733-1
	PLA2G6	NM_001004426.3		c.*81G>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.*81G>T		3_prime_UTR	Exon 17 of 17	ENSP00000333142.3	O60733-1
	PLA2G6	ENST00000402064.5	TSL:1	c.*81G>T		3_prime_UTR	Exon 16 of 16	ENSP00000386100.1	O60733-2
	PLA2G6	ENST00000668949.1		c.*81G>T		3_prime_UTR	Exon 17 of 17	ENSP00000499711.1	A0A590UK51

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 486 AN: 152108 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

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: 0.000316 AC: 426 AN: 1349666 Hom.: 0 Cov.: 23 AF XY: 0.000298 AC XY: 199 AN XY: 667962

African (AFR) AF: 0.00954 AC: 292 AN: 30624

American (AMR) AF: 0.00115 AC: 41 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24930

East Asian (EAS) AF: 0.00 AC: 0 AN: 35544

South Asian (SAS) AF: 0.0000641 AC: 5 AN: 78046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48178

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4092

European-Non Finnish (NFE) AF: 0.0000328 AC: 34 AN: 1036376

Other (OTH) AF: 0.000943 AC: 53 AN: 56218

GnomAD4 genome AF: 0.00322 AC: 490 AN: 152226 Hom.: 3 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74428

African (AFR) AF: 0.0110 AC: 457 AN: 41552

American (AMR) AF: 0.00164 AC: 25 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67992

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00257 Hom.: 0

Bravo AF: 0.00362

Asia WGS AF: 0.00346 AC: 12 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	-0.76
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		0.48

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: rs112920700; hg19: chr22-38508087;