rs3736963

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics

PLXNA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PLXNA2	NM_025179.4 link	c.4863C>T	p.Tyr1621Tyr	splice_region_variant, synonymous_variant	Exon 27 of 32	ENST00000367033.4	NP_079455.3	O75051-1
PLXNA2	XM_005273164.4 link	c.4908C>T	p.Tyr1636Tyr	splice_region_variant, synonymous_variant	Exon 27 of 33		XP_005273221.1
PLXNA2	XM_005273165.5 link	c.4908C>T	p.Tyr1636Tyr	splice_region_variant, synonymous_variant	Exon 27 of 31		XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4 link	c.4863C>T	p.Tyr1621Tyr	splice_region_variant, synonymous_variant	Exon 27 of 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

GnomAD2 exomes

AF:

0.507

AC:

127438

AN:

251200

AF XY:

0.504

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 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

African (AFR)

AF:

0.560

AC:

18631

AN:

33280

American (AMR)

AF:

0.437

AC:

19541

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

13504

AN:

26056

East Asian (EAS)

AF:

0.273

AC:

10812

AN:

39640

South Asian (SAS)

AF:

0.350

AC:

30126

AN:

86060

European-Finnish (FIN)

AF:

0.591

AC:

31539

AN:

53322

Middle Eastern (MID)

AF:

0.541

AC:

3105

AN:

5740

European-Non Finnish (NFE)

AF:

0.584

AC:

644027

AN:

1102034

Other (OTH)

AF:

0.541

AC:

32467

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15843

31685

47528

63370

79213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17392

34784

52176

69568

86960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.552

AC:

83867

AN:

152060

Hom.:

23647

Cov.:

AF XY:

0.545

AC XY:

40480

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.557

AC:

23077

AN:

41464

American (AMR)

AF:

0.505

AC:

7710

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1769

AN:

3468

East Asian (EAS)

AF:

0.252

AC:

1304

AN:

5180

South Asian (SAS)

AF:

0.343

AC:

1652

AN:

4810

European-Finnish (FIN)

AF:

0.584

AC:

6173

AN:

10572

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.593

AC:

40299

AN:

67982

Other (OTH)

AF:

0.552

AC:

1165

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1921

3843

5764

7686

9607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.568

Hom.:

86266

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PLXNA2-related disorder

Benign:1

Apr 11, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.60

PhyloP100

-0.87

Mutation Taster

=62/38

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over