rs2767565

Positions:

• chr1-208056776-G-A
• chr1-208056776-G-C

Variant summary

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

The NM_025179.4(PLXNA2):​c.2739-2238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,142 control chromosomes in the GnomAD database, including 1,884 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 (1884 hom., cov: 32)
• Consequence: PLXNA2 NM_025179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA2	NM_025179.4	c.2739-2238C>T		intron_variant		ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4	c.2784-2238C>T		intron_variant			XP_005273221.1
PLXNA2	XM_005273165.5	c.2784-2238C>T		intron_variant			XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4	c.2739-2238C>T		intron_variant		1	NM_025179.4	ENSP00000356000	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21166 AN: 152024 Hom.: 1886 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.139 AC: 21174 AN: 152142 Hom.: 1884 Cov.: 32 AF XY: 0.144 AC XY: 10677 AN XY: 74360

Gnomad4 AFR AF: 0.0405

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.162

Alfa AF: 0.144 Hom.: 213

Bravo AF: 0.132

Asia WGS AF: 0.279 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.63

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: rs2767565; hg19: chr1-208230121;