1-208065831-A-G

Variant names:

• chr1-208065831-A-G
• rs6656034
• NM_025179.4:c.2587-4994T>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.2587-4994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,070 control chromosomes in the GnomAD database, including 31,781 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 0.64 (31781 hom., cov: 32)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNA2	NM_025179.4	c.2587-4994T>C		intron_variant	Intron 12 of 31	ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4	c.2632-4994T>C		intron_variant	Intron 12 of 32		XP_005273221.1
PLXNA2	XM_005273165.5	c.2632-4994T>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.2587-4994T>C		intron_variant	Intron 12 of 31	1	NM_025179.4	ENSP00000356000.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97929 AN: 151952 Hom.: 31755 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.645 AC: 98024 AN: 152070 Hom.: 31781 Cov.: 32 AF XY: 0.641 AC XY: 47673 AN XY: 74320

African (AFR) AF: 0.622 AC: 25797 AN: 41476

American (AMR) AF: 0.574 AC: 8778 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2457 AN: 3470

East Asian (EAS) AF: 0.531 AC: 2738 AN: 5156

South Asian (SAS) AF: 0.605 AC: 2919 AN: 4828

European-Finnish (FIN) AF: 0.642 AC: 6781 AN: 10568

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46198 AN: 67972

Other (OTH) AF: 0.676 AC: 1430 AN: 2114

Alfa AF: 0.668 Hom.: 43442

Bravo AF: 0.638

Asia WGS AF: 0.552 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.84
PhyloP100		-0.60
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: rs6656034; hg19: chr1-208239176;