rs4838858

chr22-50174664-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052839.4(PANX2):c.227-2275C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,286 control chromosomes in the GnomAD database, including 941 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 0.11 (941 hom., cov: 34)
• Consequence: PANX2 NM_052839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PANX2	NM_052839.4	c.227-2275C>T		intron_variant		ENST00000395842.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PANX2	ENST00000395842.3	c.227-2275C>T		intron_variant		2	NM_052839.4	P2
PANX2	ENST00000159647.9	c.227-2275C>T		intron_variant		1		A2
PANX2	ENST00000402472.2	c.197-768C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16169 AN: 152168 Hom.: 937 Cov.: 34

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.113

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16182 AN: 152286 Hom.: 941 Cov.: 34 AF XY: 0.110 AC XY: 8217 AN XY: 74472

Gnomad4 AFR AF: 0.0820

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.0792

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.114

Alfa AF: 0.107 Hom.: 736

Bravo AF: 0.109

Asia WGS AF: 0.158 AC: 547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	8.3
Dann	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs4838858; hg19: chr22-50613093; COSMIC: COSV50292882;