dbSNP rs716461: PLXNA2: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PLXNA2	NM_025179.4 link	c.2298+96C>T	intron_variant	Intron 10 of 31	ENST00000367033.4	NP_079455.3
PLXNA2	XM_005273164.4 link	c.2343+96C>T	intron_variant	Intron 10 of 32		XP_005273221.1
PLXNA2	XM_005273165.5 link	c.2343+96C>T	intron_variant	Intron 10 of 30		XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4 link	c.2298+96C>T		intron_variant	Intron 10 of 31	1	NM_025179.4	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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over