Variant 22-50177889-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052839.4(PANX2):c.1177G>A(p.Ala393Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000519 in 1,542,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

PANX2
NM_052839.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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:

PANX2 (HGNC:):

PANX2 links:

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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=0.09082028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANX2	NM_052839.4 linkuse as main transcript	c.1177G>A	p.Ala393Thr	missense_variant	2/3	ENST00000395842.3	NP_443071.2	Q96RD6-3B3KTT7Q495U3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PANX2	ENST00000395842.3 linkuse as main transcript	c.1177G>A	p.Ala393Thr	missense_variant	2/3	2	NM_052839.4	ENSP00000379183.2	Q96RD6-3
PANX2	ENST00000159647.9 linkuse as main transcript	c.1177G>A	p.Ala393Thr	missense_variant	2/4	1		ENSP00000159647.5	Q96RD6-1
PANX2	ENST00000402472.2 linkuse as main transcript	n.*964G>A		non_coding_transcript_exon_variant	3/5	2		ENSP00000384148.2	F8W8Y4
PANX2	ENST00000402472.2 linkuse as main transcript	n.*964G>A		3_prime_UTR_variant	3/5	2		ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000504

AC:

AN:

1390112

Hom.:

Cov.:

AF XY:

0.00000583

AC XY:

AN XY:

686556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000899

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.1177G>A (p.A393T) alteration is located in exon 2 (coding exon 2) of the PANX2 gene. This alteration results from a G to A substitution at nucleotide position 1177, causing the alanine (A) at amino acid position 393 to be replaced by a threonine (T). 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

0.065

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.030

Sift

Benign

0.26

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0040

B;B

Vest4

0.14

MutPred

0.21

Gain of glycosylation at A393 (P = 0.0051);Gain of glycosylation at A393 (P = 0.0051);

MVP

0.048

MPC

1.4

ClinPred

0.24

GERP RS

3.3

Varity_R

0.051

gMVP

0.58

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