dbSNP rs149124212: PLXNB2:p.Glu1804Lys (chr22-50275891-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012401.4(PLXNB2):c.5410G>A(p.Glu1804Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,612,508 control chromosomes in the GnomAD database, including 40 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 36 hom. )

Consequence

PLXNB2
NM_012401.4 missense, splice_region

Scores

Splicing: ADA: 0.5825

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.50

Publications

10 publications found

Variant links:

Genes affected

PLXNB2 (HGNC:9104): (plexin B2) Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

PLXNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011214137).

BP6

Variant 22-50275891-C-T is Benign according to our data. Variant chr22-50275891-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653374.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00307 (467/152244) while in subpopulation SAS AF = 0.00851 (41/4820). AF 95% confidence interval is 0.00644. There are 4 homozygotes in GnomAd4. There are 227 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXNB2	NM_012401.4 link	c.5410G>A	p.Glu1804Lys	missense_variant, splice_region_variant	Exon 36 of 37	ENST00000359337.9	NP_036533.2	O15031

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXNB2	ENST00000359337.9 link	c.5410G>A	p.Glu1804Lys	missense_variant, splice_region_variant	Exon 36 of 37	5	NM_012401.4	ENSP00000352288.4		O15031

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

465

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00460

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00403

AC:

997

AN:

247586

AF XY:

0.00451

show subpopulations

Gnomad AFR exome

AF:

0.000917

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.000703

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00354

Gnomad NFE exome

AF:

0.00493

Gnomad OTH exome

AF:

0.00466

GnomAD4 exome

AF:

0.00411

AC:

5999

AN:

1460264

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

3186

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33474

American (AMR)

AF:

0.00152

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.000880

AC:

AN:

26122

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00918

AC:

792

AN:

86250

European-Finnish (FIN)

AF:

0.00361

AC:

188

AN:

52094

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00422

AC:

4687

AN:

1111792

Other (OTH)

AF:

0.00315

AC:

190

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

325

649

974

1298

1623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00307

AC:

467

AN:

152244

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41542

American (AMR)

AF:

0.00196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00851

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00460

AC:

313

AN:

68016

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.00235

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000500

AC:

ESP6500EA

AF:

0.00301

AC:

ExAC

AF:

0.00446

AC:

536

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PLXNB2: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;.

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;M

PhyloP100

2.5

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.020

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.99

D;D

Vest4

0.62

MVP

0.30

MPC

1.7

ClinPred

0.025

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.12

gMVP

0.46

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.58

dbscSNV1_RF

Benign

0.71

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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rs149124212

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