22-50178377-A-G

Variant names:

• chr22-50178377-A-G
• rs5771206
• NM_052839.4:c.1665A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_052839.4(PANX2):​c.1665A>G​(p.Leu555Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,448,638 control chromosomes in the GnomAD database, including 297,179 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28613 hom., cov: 34)
  • Exomes 𝑓: 0.64 (268566 hom.)
• Consequence: PANX2 NM_052839.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 17 publications found

Genes affected

PANX2 (HGNC:8600): (pannexin 2) The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 1 are abundantly expressed in central nervous system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 1 may form cell type-specific gap junctions with distinct properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=0.638 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052839.4. 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
	PANX2	NM_052839.4	MANE Select	c.1665A>G	p.Leu555Leu	synonymous	Exon 2 of 3	NP_443071.2	Q96RD6-3
	PANX2	NM_001160300.2		c.1665A>G	p.Leu555Leu	synonymous	Exon 2 of 4	NP_001153772.1	Q96RD6-1
	PANX2	NR_027691.2		n.1716A>G		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANX2	ENST00000395842.3	TSL:2 MANE Select	c.1665A>G	p.Leu555Leu	synonymous	Exon 2 of 3	ENSP00000379183.2	Q96RD6-3
	PANX2	ENST00000159647.9	TSL:1	c.1665A>G	p.Leu555Leu	synonymous	Exon 2 of 4	ENSP00000159647.5	Q96RD6-1
	PANX2	ENST00000402472.2	TSL:2	n.*1452A>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92650 AN: 151910 Hom.: 28591 Cov.: 34

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.603

GnomAD2 exomes AF: 0.583 AC: 33754 AN: 57908 AF XY: 0.582

Gnomad AFR exome AF: 0.496

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.605

Gnomad EAS exome AF: 0.453

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.641

Gnomad OTH exome AF: 0.607

GnomAD4 exome AF: 0.642 AC: 832378 AN: 1296608 Hom.: 268566 Cov.: 36 AF XY: 0.639 AC XY: 405775 AN XY: 635444

African (AFR) AF: 0.546 AC: 13945 AN: 25522

American (AMR) AF: 0.521 AC: 9821 AN: 18846

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 12003 AN: 19820

East Asian (EAS) AF: 0.488 AC: 15559 AN: 31880

South Asian (SAS) AF: 0.570 AC: 37738 AN: 66198

European-Finnish (FIN) AF: 0.659 AC: 24432 AN: 37072

Middle Eastern (MID) AF: 0.595 AC: 2218 AN: 3728

European-Non Finnish (NFE) AF: 0.657 AC: 683010 AN: 1040156

Other (OTH) AF: 0.630 AC: 33652 AN: 53386

GnomAD4 genome AF: 0.610 AC: 92722 AN: 152030 Hom.: 28613 Cov.: 34 AF XY: 0.610 AC XY: 45310 AN XY: 74314

African (AFR) AF: 0.549 AC: 22790 AN: 41488

American (AMR) AF: 0.572 AC: 8745 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2098 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2543 AN: 5118

South Asian (SAS) AF: 0.567 AC: 2737 AN: 4828

European-Finnish (FIN) AF: 0.686 AC: 7256 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44580 AN: 67940

Other (OTH) AF: 0.599 AC: 1265 AN: 2112

Alfa AF: 0.616 Hom.: 7207

Bravo AF: 0.596

Asia WGS AF: 0.533 AC: 1851 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		0.64
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: rs5771206; hg19: chr22-50616806; COSMIC: COSV50291673;