22-50177272-T-G

Position:

• chr22-50177272-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_052839.4(PANX2):​c.560T>G​(p.Ile187Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PANX2	NM_052839.4	c.560T>G	p.Ile187Ser	missense_variant	2/3	ENST00000395842.3	NP_443071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PANX2	ENST00000395842.3	c.560T>G	p.Ile187Ser	missense_variant	2/3	2	NM_052839.4	ENSP00000379183.2
PANX2	ENST00000159647.9	c.560T>G	p.Ile187Ser	missense_variant	2/4	1		ENSP00000159647.5
PANX2	ENST00000402472.2	n.*347T>G		non_coding_transcript_exon_variant	3/5	2		ENSP00000384148.2
PANX2	ENST00000402472.2	n.*347T>G		3_prime_UTR_variant	3/5	2		ENSP00000384148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

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

Apr 09, 2024

The c.560T>G (p.I187S) alteration is located in exon 2 (coding exon 2) of the PANX2 gene. This alteration results from a T to G substitution at nucleotide position 560, causing the isoleucine (I) at amino acid position 187 to be replaced by a serine (S). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.64	N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.76	N;N
REVEL	Uncertain	0.56
Sift	Benign	0.043	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.92
MutPred		0.44		Gain of phosphorylation at I187 (P = 0.0025);Gain of phosphorylation at I187 (P = 0.0025);
MVP		0.30
MPC		3.0
ClinPred		0.89	D
GERP RS		4.8
Varity_R		0.35
gMVP		0.94

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: chr22-50615701; COSMIC: COSV50305117;