22-50178375-C-T

Variant names:

• chr22-50178375-C-T
• rs1199661100
• NM_052839.4:c.1663C>T
• PANX2 p.Leu555Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_052839.4(PANX2):​c.1663C>T​(p.Leu555Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,307,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PANX2 NM_052839.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.407 with no splicing effect.

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.1663C>T	p.Leu555Leu	synonymous	Exon 2 of 3	NP_443071.2	Q96RD6-3
	PANX2	NM_001160300.2		c.1663C>T	p.Leu555Leu	synonymous	Exon 2 of 4	NP_001153772.1	Q96RD6-1
	PANX2	NR_027691.2		n.1714C>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.1663C>T	p.Leu555Leu	synonymous	Exon 2 of 3	ENSP00000379183.2	Q96RD6-3
	PANX2	ENST00000159647.9	TSL:1	c.1663C>T	p.Leu555Leu	synonymous	Exon 2 of 4	ENSP00000159647.5	Q96RD6-1
	PANX2	ENST00000402472.2	TSL:2	n.*1450C>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000384148.2	F8W8Y4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1307610 Hom.: 0 Cov.: 38 AF XY: 0.00000156 AC XY: 1 AN XY: 641242

African (AFR) AF: 0.00 AC: 0 AN: 26000

American (AMR) AF: 0.00 AC: 0 AN: 20350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20290

East Asian (EAS) AF: 0.00 AC: 0 AN: 32450

South Asian (SAS) AF: 0.00 AC: 0 AN: 67692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3796

European-Non Finnish (NFE) AF: 9.57e-7 AC: 1 AN: 1045012

Other (OTH) AF: 0.0000186 AC: 1 AN: 53900

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.77
PhyloP100		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1199661100;

hg19: chr22-50616804;