chr22-50178377-A-C

Variant names:

• chr22-50178377-A-C
• rs5771206
• NM_052839.4:c.1665A>C

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.1665A>C​(p.Leu555Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PANX2 NM_052839.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638
• Publications: 17 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=-0.94).
• BP7: Synonymous conserved (PhyloP=0.638 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX2	NM_052839.4	c.1665A>C	p.Leu555Leu	synonymous_variant	Exon 2 of 3	ENST00000395842.3	NP_443071.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX2	ENST00000395842.3	c.1665A>C	p.Leu555Leu	synonymous_variant	Exon 2 of 3	2	NM_052839.4	ENSP00000379183.2
PANX2	ENST00000159647.9	c.1665A>C	p.Leu555Leu	synonymous_variant	Exon 2 of 4	1		ENSP00000159647.5
PANX2	ENST00000402472.2	n.*1452A>C		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000384148.2
PANX2	ENST00000402472.2	n.*1452A>C		3_prime_UTR_variant	Exon 3 of 5	2		ENSP00000384148.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1298664 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 636476

African (AFR) AF: 0.00 AC: 0 AN: 25558

American (AMR) AF: 0.00 AC: 0 AN: 18960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19850

East Asian (EAS) AF: 0.00 AC: 0 AN: 31956

South Asian (SAS) AF: 0.00 AC: 0 AN: 66348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041656

Other (OTH) AF: 0.00 AC: 0 AN: 53468

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		0.64

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: rs5771206; hg19: chr22-50616806;