Variant rs3736963 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025179.4(PLXNA2):c.4863C>T(p.Tyr1621Tyr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,602,934 control chromosomes in the GnomAD database, including 251,313 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23647 hom., cov: 32)

Exomes 𝑓: 0.55 ( 227666 hom. )

Consequence

PLXNA2
NM_025179.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0007056

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.867

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-208034494-G-A is Benign according to our data. Variant chr1-208034494-G-A is described in ClinVar as [Benign]. Clinvar id is 1164720.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.867 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXNA2	NM_025179.4 linkuse as main transcript	c.4863C>T	p.Tyr1621Tyr	splice_region_variant, synonymous_variant	27/32	ENST00000367033.4	NP_079455.3	O75051-1
PLXNA2	XM_005273164.4 linkuse as main transcript	c.4908C>T	p.Tyr1636Tyr	splice_region_variant, synonymous_variant	27/33		XP_005273221.1
PLXNA2	XM_005273165.5 linkuse as main transcript	c.4908C>T	p.Tyr1636Tyr	splice_region_variant, synonymous_variant	27/31		XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4 linkuse as main transcript	c.4863C>T	p.Tyr1621Tyr	splice_region_variant, synonymous_variant	27/32	1	NM_025179.4	ENSP00000356000.3		O75051-1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83827

AN:

151944

Hom.:

23643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.598

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.593

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.507

AC:

127438

AN:

251200

Hom.:

34058

AF XY:

0.504

AC XY:

68437

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.554

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.348

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.588

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.554

AC:

803752

AN:

1450874

Hom.:

227666

Cov.:

AF XY:

0.549

AC XY:

396454

AN XY:

722364

show subpopulations

Gnomad4 AFR exome

AF:

0.560

Gnomad4 AMR exome

AF:

0.437

Gnomad4 ASJ exome

AF:

0.518

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.591

Gnomad4 NFE exome

AF:

0.584

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.552

AC:

83867

AN:

152060

Hom.:

23647

Cov.:

AF XY:

0.545

AC XY:

40480

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.557

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.593

Gnomad4 OTH

AF:

0.552

Alfa

AF:

0.572

Hom.:

55043

Bravo

AF:

0.547

Asia WGS

AF:

0.305

AC:

1066

AN:

3478

EpiCase

AF:

0.587

EpiControl

AF:

0.584

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

PLXNA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.1

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00071

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over