1-208064332-A-G

Variant names:

• chr1-208064332-A-G
• rs752016
• NM_025179.4:c.2587-3495T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025179.4(PLXNA2):​c.2587-3495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,200 control chromosomes in the GnomAD database, including 2,532 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 0.16 (2532 hom., cov: 33)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.909
• Publications: 20 publications found

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]

PLXNA2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA2	NM_025179.4	c.2587-3495T>C		intron_variant	Intron 12 of 31	ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4	c.2632-3495T>C		intron_variant	Intron 12 of 32		XP_005273221.1
PLXNA2	XM_005273165.5	c.2632-3495T>C		intron_variant	Intron 12 of 30		XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2587-3495T>C		intron_variant	Intron 12 of 31	1	NM_025179.4	ENSP00000356000.3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24542 AN: 152082 Hom.: 2537 Cov.: 33

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.161 AC: 24536 AN: 152200 Hom.: 2532 Cov.: 33 AF XY: 0.165 AC XY: 12272 AN XY: 74410

African (AFR) AF: 0.0619 AC: 2572 AN: 41548

American (AMR) AF: 0.200 AC: 3053 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2287 AN: 5158

South Asian (SAS) AF: 0.333 AC: 1606 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1624 AN: 10604

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11936 AN: 68002

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.168 Hom.: 4642

Bravo AF: 0.162

Asia WGS AF: 0.349 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.76
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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: rs752016; hg19: chr1-208237677;