chr22-50177893-C-T

Variant names:

• chr22-50177893-C-T
• rs199548028
• NM_052839.4:c.1181C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_052839.4(PANX2):​c.1181C>T​(p.Thr394Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,538,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00037 (1 hom.)
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1815922).

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.1181C>T	p.Thr394Ile	missense	Exon 2 of 3	NP_443071.2	Q96RD6-3
	PANX2	NM_001160300.2		c.1181C>T	p.Thr394Ile	missense	Exon 2 of 4	NP_001153772.1	Q96RD6-1
	PANX2	NR_027691.2		n.1232C>T		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANX2	ENST00000395842.3	TSL:2 MANE Select	c.1181C>T	p.Thr394Ile	missense	Exon 2 of 3	ENSP00000379183.2	Q96RD6-3
	PANX2	ENST00000159647.9	TSL:1	c.1181C>T	p.Thr394Ile	missense	Exon 2 of 4	ENSP00000159647.5	Q96RD6-1
	PANX2	ENST00000402472.2	TSL:2	n.*968C>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152138 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000315 AC: 44 AN: 139594 AF XY: 0.000378

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000409

Gnomad ASJ exome AF: 0.000130

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000765

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000366 AC: 507 AN: 1385890 Hom.: 1 Cov.: 33 AF XY: 0.000358 AC XY: 245 AN XY: 684094

African (AFR) AF: 0.00 AC: 0 AN: 31850

American (AMR) AF: 0.0000278 AC: 1 AN: 35950

Ashkenazi Jewish (ASJ) AF: 0.0000403 AC: 1 AN: 24790

East Asian (EAS) AF: 0.00 AC: 0 AN: 36186

South Asian (SAS) AF: 0.00 AC: 0 AN: 80574

European-Finnish (FIN) AF: 0.000289 AC: 10 AN: 34648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 0.000448 AC: 483 AN: 1078350

Other (OTH) AF: 0.000207 AC: 12 AN: 57884

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152138 Hom.: 0 Cov.: 34 AF XY: 0.000552 AC XY: 41 AN XY: 74322

African (AFR) AF: 0.0000965 AC: 4 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00121 Hom.: 0

Bravo AF: 0.000325

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000359 AC: 3

ExAC AF: 0.000237 AC: 26

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.76
MVP		0.15
MPC		2.3
ClinPred		0.17	T
GERP RS		4.3
Varity_R		0.37
gMVP		0.90
Mutation Taster		=40/60	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

dbSNP: rs199548028; hg19: chr22-50616322; COSMIC: COSV99031008;