chr22-50170774-T-C

Variant names:

• chr22-50170774-T-C
• NM_052839.4:c.44T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_052839.4(PANX2):​c.44T>C​(p.Leu15Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43
• 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 2 ACMG points.

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

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.44T>C	p.Leu15Pro	missense	Exon 1 of 3	NP_443071.2	Q96RD6-3
	PANX2	NM_001160300.2		c.44T>C	p.Leu15Pro	missense	Exon 1 of 4	NP_001153772.1	Q96RD6-1
	PANX2	NR_027691.2		n.44T>C		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.44T>C	p.Leu15Pro	missense	Exon 1 of 3	ENSP00000379183.2	Q96RD6-3
	PANX2	ENST00000159647.9	TSL:1	c.44T>C	p.Leu15Pro	missense	Exon 1 of 4	ENSP00000159647.5	Q96RD6-1
	PANX2	ENST00000402472.2	TSL:2	n.14T>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1231404 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 601342

African (AFR) AF: 0.00 AC: 0 AN: 25378

American (AMR) AF: 0.00 AC: 0 AN: 19512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18888

East Asian (EAS) AF: 0.00 AC: 0 AN: 27430

South Asian (SAS) AF: 0.00 AC: 0 AN: 59054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39908

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 988562

Other (OTH) AF: 0.00 AC: 0 AN: 48992

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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Benign	0.85
DEOGEN2	Benign	0.044	T
Eigen	Benign	0.0010
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.4
PrimateAI	Pathogenic	0.97	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.69
MutPred		0.60		Gain of loop (P = 0.0051)
MVP		0.22
MPC		2.7
ClinPred		0.70	D
GERP RS		2.8
PromoterAI		-0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.68
gMVP		0.91
Mutation Taster		=11/89	disease causing

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: chr22-50609203;