Genetic Variant PANX2:p.Phe123Leu (chr22-50177081-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_052839.4(PANX2):c.369C>G(p.Phe123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: not found (cov: 34)

Consequence

PANX2
NM_052839.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.34

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20470563).

BP6

Variant 22-50177081-C-G is Benign according to our data. Variant chr22-50177081-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2534387.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PANX2	NM_052839.4	MANE Select	c.369C>G	p.Phe123Leu	missense	Exon 2 of 3	NP_443071.2	Q96RD6-3
PANX2	NM_001160300.2		c.369C>G	p.Phe123Leu	missense	Exon 2 of 4	NP_001153772.1	Q96RD6-1
PANX2	NR_027691.2		n.420C>G		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PANX2	ENST00000395842.3	TSL:2 MANE Select	c.369C>G	p.Phe123Leu	missense	Exon 2 of 3	ENSP00000379183.2	Q96RD6-3
PANX2	ENST00000159647.9	TSL:1	c.369C>G	p.Phe123Leu	missense	Exon 2 of 4	ENSP00000159647.5	Q96RD6-1
PANX2	ENST00000402472.2	TSL:2	n.*156C>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.16

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.013

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

1.3

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.099

Sift

Benign

0.13

Sift4G

Benign

0.098

Polyphen

0.0010

Vest4

0.28

MutPred

0.76

Loss of methylation at K122 (P = 0.1282)

MVP

0.20

MPC

1.5

ClinPred

0.64

GERP RS

2.3

Varity_R

0.26

gMVP

0.65

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over