22-50170750-A-T

Position:

• chr22-50170750-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052839.4(PANX2):​c.20A>T​(p.Gln7Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.427

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 (HGNC:):

ACMG classification

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=0.1783346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANX2	NM_052839.4	c.20A>T	p.Gln7Leu	missense_variant	1/3	ENST00000395842.3	NP_443071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANX2	ENST00000395842.3	c.20A>T	p.Gln7Leu	missense_variant	1/3	2	NM_052839.4	ENSP00000379183.2
PANX2	ENST00000159647.9	c.20A>T	p.Gln7Leu	missense_variant	1/4	1		ENSP00000159647.5
PANX2	ENST00000402472.2	n.-11A>T		upstream_gene_variant		2		ENSP00000384148.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.20A>T (p.Q7L) alteration is located in exon 1 (coding exon 1) of the PANX2 gene. This alteration results from a A to T substitution at nucleotide position 20, causing the glutamine (Q) at amino acid position 7 to be replaced by a leucine (L). 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	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.46	T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.045
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.11	B;B
Vest4		0.47
MutPred		0.15		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.072
MPC		1.3
ClinPred		0.25	T
GERP RS		1.3
Varity_R		0.14
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50609179;