chr22-50170896-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052839.4(PANX2):c.166A>G(p.Ile56Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000216 in 1,525,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PANX2
NM_052839.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Variant links:

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]

PANX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09346157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX2	NM_052839.4 link	c.166A>G	p.Ile56Val	missense_variant	Exon 1 of 3	ENST00000395842.3	NP_443071.2	Q96RD6-3B3KTT7Q495U3
PANX2	NM_001160300.2 link	c.166A>G	p.Ile56Val	missense_variant	Exon 1 of 4		NP_001153772.1	Q96RD6-1
PANX2	XM_047441448.1 link	c.-288A>G		5_prime_UTR_variant	Exon 1 of 4		XP_047297404.1
PANX2	NR_027691.2 link	n.166A>G		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PANX2	ENST00000395842.3 link	c.166A>G	p.Ile56Val	missense_variant	Exon 1 of 3	2	NM_052839.4	ENSP00000379183.2	Q96RD6-3
PANX2	ENST00000159647.9 link	c.166A>G	p.Ile56Val	missense_variant	Exon 1 of 4	1		ENSP00000159647.5	Q96RD6-1
PANX2	ENST00000402472.2 link	n.136A>G		non_coding_transcript_exon_variant	Exon 1 of 5	2		ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000357

AC:

AN:

168194

Hom.:

AF XY:

0.0000422

AC XY:

AN XY:

94706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000211

AC:

AN:

1373292

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

682326

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000176

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000206

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000671

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000836

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166A>G (p.I56V) alteration is located in exon 1 (coding exon 1) of the PANX2 gene. This alteration results from a A to G substitution at nucleotide position 166, causing the isoleucine (I) at amino acid position 56 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Benign

0.92

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.098

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.058

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.068

Sift

Benign

0.13

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.055

B;B

Vest4

0.33

MVP

0.17

MPC

1.4

ClinPred

0.14

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over