22-38111973-AGGCGG-A

Position:

• chr22-38111973-AGGCGG-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003560.4(PLA2G6):​c.*183_*187del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 651,406 control chromosomes in the GnomAD database, including 2,586 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (428 hom., cov: 31)
  • Exomes 𝑓: 0.084 (2158 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.292

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 22-38111973-AGGCGG-A is Benign according to our data. Variant chr22-38111973-AGGCGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 341632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.*183_*187del		3_prime_UTR_variant	17/17	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.*183_*187del		3_prime_UTR_variant	17/17	1	NM_003560.4	ENSP00000333142	P3

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10034 AN: 152124 Hom.: 427 Cov.: 31

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0779

GnomAD4 exome AF: 0.0836 AC: 41750 AN: 499164 Hom.: 2158 AF XY: 0.0833 AC XY: 22027 AN XY: 264408

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.0517

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.0762

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.0707

Gnomad4 OTH exome AF: 0.0818

GnomAD4 genome AF: 0.0659 AC: 10039 AN: 152242 Hom.: 428 Cov.: 31 AF XY: 0.0688 AC XY: 5119 AN XY: 74434

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0688 Hom.: 59

Bravo AF: 0.0587

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Infantile neuroaxonal dystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139718702; hg19: chr22-38507980;