rs2478813

Positions:

• chr1-208073865-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000367033.4(PLXNA2):​c.2586+5395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,068 control chromosomes in the GnomAD database, including 54,208 homozygotes. 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: 𝑓 0.84 (54208 hom., cov: 30)
• Consequence: PLXNA2 ENST00000367033.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775

Genes affected

PLXNA2 (HGNC:9100): (plexin A2) This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA2	NM_025179.4	c.2586+5395T>C		intron_variant		ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4	c.2631+5395T>C		intron_variant			XP_005273221.1
PLXNA2	XM_005273165.5	c.2631+5395T>C		intron_variant			XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2586+5395T>C		intron_variant		1	NM_025179.4	ENSP00000356000	P1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128029 AN: 151950 Hom.: 54175 Cov.: 30

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.835

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.843 AC: 128120 AN: 152068 Hom.: 54208 Cov.: 30 AF XY: 0.840 AC XY: 62490 AN XY: 74354

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.819

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.833

Alfa AF: 0.863 Hom.: 7062

Bravo AF: 0.839

Asia WGS AF: 0.712 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.80
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2478813; hg19: chr1-208247210;