rs716461

chr1-208084284-G-A

Variant summary

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

The NM_025179.4(PLXNA2):c.2298+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,312,566 control chromosomes in the GnomAD database, including 47,821 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 0.23 (4301 hom., cov: 32)
  • Exomes 𝑓: 0.27 (43520 hom.)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA2	NM_025179.4	c.2298+96C>T		intron_variant		ENST00000367033.4
PLXNA2	XM_005273164.4	c.2343+96C>T		intron_variant
PLXNA2	XM_005273165.5	c.2343+96C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2298+96C>T		intron_variant		1	NM_025179.4	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34650 AN: 151960 Hom.: 4306 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.271 AC: 314151 AN: 1160488 Hom.: 43520 AF XY: 0.271 AC XY: 158149 AN XY: 583564

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.228 AC: 34654 AN: 152078 Hom.: 4301 Cov.: 32 AF XY: 0.230 AC XY: 17058 AN XY: 74324

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.201

Alfa AF: 0.260 Hom.: 2519

Bravo AF: 0.225

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.9
Dann	Benign	0.46

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: rs716461; hg19: chr1-208257629; COSMIC: COSV65446537;