chr22-50170750-A-T

Variant names:

• chr22-50170750-A-T
• NM_052839.4:c.20A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1783346).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANX2	NM_052839.4	MANE Select	c.20A>T	p.Gln7Leu	missense	Exon 1 of 3	NP_443071.2	Q96RD6-3
	PANX2	NM_001160300.2		c.20A>T	p.Gln7Leu	missense	Exon 1 of 4	NP_001153772.1	Q96RD6-1
	PANX2	NR_027691.2		n.20A>T		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANX2	ENST00000395842.3	TSL:2 MANE Select	c.20A>T	p.Gln7Leu	missense	Exon 1 of 3	ENSP00000379183.2	Q96RD6-3
	PANX2	ENST00000159647.9	TSL:1	c.20A>T	p.Gln7Leu	missense	Exon 1 of 4	ENSP00000159647.5	Q96RD6-1
	PANX2	ENST00000402472.2	TSL:2	n.-11A>T		upstream_gene	N/A	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.43
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.045
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.030	D
Polyphen		0.11	B
Vest4		0.47
MutPred		0.15		Loss of helix (P = 0.0558)
MVP		0.072
MPC		1.3
ClinPred		0.25	T
GERP RS		1.3
PromoterAI		-0.032	Neutral
Varity_R		0.14
gMVP		0.66
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr22-50609179;