rs841865

Positions:

• chr1-208052564-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.2857-101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,182,516 control chromosomes in the GnomAD database, including 19,516 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 0.14 (1881 hom., cov: 32)
  • Exomes 𝑓: 0.18 (17635 hom.)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA2	NM_025179.4	c.2857-101C>T		intron_variant		ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4	c.2902-101C>T		intron_variant			XP_005273221.1
PLXNA2	XM_005273165.5	c.2902-101C>T		intron_variant			XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2857-101C>T		intron_variant		1	NM_025179.4	ENSP00000356000	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21079 AN: 152036 Hom.: 1884 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.178 AC: 183064 AN: 1030362 Hom.: 17635 AF XY: 0.181 AC XY: 94138 AN XY: 520586

Gnomad4 AFR exome AF: 0.0307

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.303

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.139 AC: 21082 AN: 152154 Hom.: 1881 Cov.: 32 AF XY: 0.143 AC XY: 10642 AN XY: 74374

Gnomad4 AFR AF: 0.0379

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.162

Alfa AF: 0.168 Hom.: 4326

Bravo AF: 0.131

Asia WGS AF: 0.277 AC: 961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.37

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: rs841865; hg19: chr1-208225909; COSMIC: COSV65440377;