22-50177820-G-C

Variant names:

• chr22-50177820-G-C
• rs759446317
• NM_052839.4:c.1108G>C

Variant summary

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

The NM_052839.4(PANX2):​c.1108G>C​(p.Glu370Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.47

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX2	NM_052839.4	c.1108G>C	p.Glu370Gln	missense_variant	Exon 2 of 3	ENST00000395842.3	NP_443071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX2	ENST00000395842.3	c.1108G>C	p.Glu370Gln	missense_variant	Exon 2 of 3	2	NM_052839.4	ENSP00000379183.2
PANX2	ENST00000159647.9	c.1108G>C	p.Glu370Gln	missense_variant	Exon 2 of 4	1		ENSP00000159647.5
PANX2	ENST00000402472.2	n.*895G>C		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000384148.2
PANX2	ENST00000402472.2	n.*895G>C		3_prime_UTR_variant	Exon 3 of 5	2		ENSP00000384148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000435 AC: 1 AN: 229956 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126804

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448156 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 720730

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.29
Sift	Benign	0.069	T;T
Sift4G	Uncertain	0.037	D;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.38		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.12
MPC		2.5
ClinPred		0.61	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.91

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

Other links and lift over

dbSNP: rs759446317; hg19: chr22-50616249;