Genetic Variant PLXNA2:c.2586+149G>A (chr1-208079111-C-T) – 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.2586+149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 633,008 control chromosomes in the GnomAD database, including 22,716 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 0.26 ( 5142 hom., cov: 32)

Exomes 𝑓: 0.26 ( 17574 hom. )

Consequence

PLXNA2
NM_025179.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.583

Publications

9 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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PLXNA2	NM_025179.4 link	c.2586+149G>A	intron_variant	Intron 12 of 31	ENST00000367033.4	NP_079455.3	O75051-1
PLXNA2	XM_005273164.4 link	c.2631+149G>A	intron_variant	Intron 12 of 32		XP_005273221.1
PLXNA2	XM_005273165.5 link	c.2631+149G>A	intron_variant	Intron 12 of 30		XP_005273222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNA2	ENST00000367033.4 link	c.2586+149G>A		intron_variant	Intron 12 of 31	1	NM_025179.4	ENSP00000356000.3		O75051-1

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38851

AN:

152008

Hom.:

5143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.265

AC:

127339

AN:

480882

Hom.:

17574

AF XY:

0.267

AC XY:

66680

AN XY:

249304

show subpopulations

African (AFR)

AF:

0.217

AC:

2846

AN:

13128

American (AMR)

AF:

0.353

AC:

6526

AN:

18512

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

3245

AN:

13446

East Asian (EAS)

AF:

0.182

AC:

5644

AN:

30948

South Asian (SAS)

AF:

0.317

AC:

13252

AN:

41760

European-Finnish (FIN)

AF:

0.233

AC:

9997

AN:

42900

Middle Eastern (MID)

AF:

0.269

AC:

557

AN:

2068

European-Non Finnish (NFE)

AF:

0.269

AC:

78401

AN:

291546

Other (OTH)

AF:

0.259

AC:

6871

AN:

26574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

4364

8727

13091

17454

21818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.255

AC:

38855

AN:

152126

Hom.:

5142

Cov.:

AF XY:

0.256

AC XY:

19016

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.218

AC:

9055

AN:

41512

American (AMR)

AF:

0.324

AC:

4957

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.231

AC:

803

AN:

3472

East Asian (EAS)

AF:

0.194

AC:

1003

AN:

5162

South Asian (SAS)

AF:

0.316

AC:

1523

AN:

4814

European-Finnish (FIN)

AF:

0.235

AC:

2488

AN:

10584

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18339

AN:

67988

Other (OTH)

AF:

0.249

AC:

526

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1462

2923

4385

5846

7308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.270

Hom.:

3615

Bravo

AF:

0.257

Asia WGS

AF:

0.287

AC:

997

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.80

(source)

DANN

Benign

0.81

PhyloP100

-0.58

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