chr1-208079111-C-T

Position:

• chr1-208079111-C-T

Variant summary

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

The NM_025179.4(PLXNA2):​c.2586+149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 633,008 control chromosomes in the GnomAD database, including 22,716 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 0.26 (5142 hom., cov: 32)
  • Exomes 𝑓: 0.26 (17574 hom.)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXNA2	NM_025179.4	c.2586+149G>A		intron_variant		ENST00000367033.4
PLXNA2	XM_005273164.4	c.2631+149G>A		intron_variant
PLXNA2	XM_005273165.5	c.2631+149G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2586+149G>A		intron_variant		1	NM_025179.4	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38851 AN: 152008 Hom.: 5143 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.265 AC: 127339 AN: 480882 Hom.: 17574 AF XY: 0.267 AC XY: 66680 AN XY: 249304

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.255 AC: 38855 AN: 152126 Hom.: 5142 Cov.: 32 AF XY: 0.256 AC XY: 19016 AN XY: 74360

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.249

Alfa AF: 0.270 Hom.: 3338

Bravo AF: 0.257

Asia WGS AF: 0.287 AC: 997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.81

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: rs2274446; hg19: chr1-208252456; COSMIC: COSV65442658;