Genetic Variant NM_025179.4:c.2298+96C>T (chr1-208084284-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025179.4(PLXNA2):c.2298+96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,312,566 control chromosomes in the GnomAD database, including 47,821 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 0.23 ( 4301 hom., cov: 32)

Exomes 𝑓: 0.27 ( 43520 hom. )

Consequence

PLXNA2
NM_025179.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.744

Publications

4 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025179.4. 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.2298+96C>T		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.2298+96C>T		intron	N/A	ENSP00000356000.3

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34650

AN:

151960

Hom.:

4306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.0969

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.271

AC:

314151

AN:

1160488

Hom.:

43520

AF XY:

0.271

AC XY:

158149

AN XY:

583564

show subpopulations

African (AFR)

AF:

0.128

AC:

3498

AN:

27336

American (AMR)

AF:

0.348

AC:

13351

AN:

38416

Ashkenazi Jewish (ASJ)

AF:

0.179

AC:

3784

AN:

21098

East Asian (EAS)

AF:

0.164

AC:

6237

AN:

38026

South Asian (SAS)

AF:

0.299

AC:

21334

AN:

71316

European-Finnish (FIN)

AF:

0.257

AC:

11218

AN:

43580

Middle Eastern (MID)

AF:

0.214

AC:

727

AN:

3390

European-Non Finnish (NFE)

AF:

0.278

AC:

241246

AN:

867364

Other (OTH)

AF:

0.255

AC:

12756

AN:

49962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11278

22557

33835

45114

56392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7544

15088

22632

30176

37720

<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:

0.228

AC:

34654

AN:

152078

Hom.:

4301

Cov.:

AF XY:

0.230

AC XY:

17058

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.136

AC:

5637

AN:

41516

American (AMR)

AF:

0.296

AC:

4529

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

588

AN:

3470

East Asian (EAS)

AF:

0.196

AC:

1008

AN:

5144

South Asian (SAS)

AF:

0.289

AC:

1386

AN:

4802

European-Finnish (FIN)

AF:

0.246

AC:

2604

AN:

10574

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18337

AN:

67966

Other (OTH)

AF:

0.201

AC:

424

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1312

2624

3936

5248

6560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.260

Hom.:

2785

Bravo

AF:

0.225

Asia WGS

AF:

0.262

AC:

910

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

(source)

DANN

Benign

0.46

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over