rs374911171

Variant names:

• chr22-50177825-C-A
• rs374911171
• NM_052839.4:c.1113C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-50177825-C-A
• chr22-50177825-C-G
• chr22-50177825-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052839.4(PANX2):​c.1113C>A​(p.Ser371Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,599,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PANX2 NM_052839.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.112
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3960293).

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.1113C>A	p.Ser371Arg	missense	Exon 2 of 3	NP_443071.2	Q96RD6-3
	PANX2	NM_001160300.2		c.1113C>A	p.Ser371Arg	missense	Exon 2 of 4	NP_001153772.1	Q96RD6-1
	PANX2	NR_027691.2		n.1164C>A		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.1113C>A	p.Ser371Arg	missense	Exon 2 of 3	ENSP00000379183.2	Q96RD6-3
	PANX2	ENST00000159647.9	TSL:1	c.1113C>A	p.Ser371Arg	missense	Exon 2 of 4	ENSP00000159647.5	Q96RD6-1
	PANX2	ENST00000402472.2	TSL:2	n.*900C>A		non_coding_transcript_exon	Exon 3 of 5	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000439 AC: 1 AN: 227710 AF XY: 0.00

Gnomad AFR exome AF: 0.0000667

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.91e-7 AC: 1 AN: 1447100 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 720232

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111084

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152218 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74368

African (AFR) AF: 0.0000724 AC: 3 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000830 AC: 1

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	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.11
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.24
Sift	Benign	0.043	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.60	P
Vest4		0.88
MutPred		0.28		Gain of helix (P = 0.0325)
MVP		0.067
MPC		2.6
ClinPred		0.61	D
GERP RS		3.0
Varity_R		0.24
gMVP		0.97
Mutation Taster		=23/77	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: rs374911171; hg19: chr22-50616254;