1-208081968-A-G

Variant names:

• chr1-208081968-A-G
• rs2498028
• NM_025179.4:c.2395+444T>C

Variant summary

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

The ENST00000367033.4(PLXNA2):​c.2395+444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,124 control chromosomes in the GnomAD database, including 1,700 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 0.13 (1700 hom., cov: 32)
• Consequence: PLXNA2 ENST00000367033.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA2	NM_025179.4	MANE Select	c.2395+444T>C		intron	N/A	NP_079455.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXNA2	ENST00000367033.4	TSL:1 MANE Select	c.2395+444T>C		intron	N/A	ENSP00000356000.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19658 AN: 152004 Hom.: 1704 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.129 AC: 19657 AN: 152124 Hom.: 1700 Cov.: 32 AF XY: 0.133 AC XY: 9878 AN XY: 74352

African (AFR) AF: 0.0314 AC: 1304 AN: 41542

American (AMR) AF: 0.127 AC: 1936 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3466

East Asian (EAS) AF: 0.337 AC: 1737 AN: 5152

South Asian (SAS) AF: 0.253 AC: 1216 AN: 4802

European-Finnish (FIN) AF: 0.141 AC: 1494 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10654 AN: 67980

Other (OTH) AF: 0.150 AC: 316 AN: 2108

Alfa AF: 0.130 Hom.: 184

Bravo AF: 0.125

Asia WGS AF: 0.271 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.62
PhyloP100		-0.69
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: rs2498028; hg19: chr1-208255313;