rs2285372

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015103.3(PLXND1):c.1849C>T(p.Pro617Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 1,613,970 control chromosomes in the GnomAD database, including 1,857 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict 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 (no stars).

Frequency

Genomes: 𝑓 0.049 ( 263 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1594 hom. )

Consequence

PLXND1
NM_015103.3 missense, splice_region

Scores

Splicing: ADA: 0.006426

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.09

Publications

13 publications found

Variant links:

Genes affected

PLXND1 (HGNC:9107): (plexin D1) Enables protein domain specific binding activity. Predicted to be involved in several processes, including endothelial cell migration; nervous system development; and regulation of angiogenesis. Predicted to act upstream of or within several processes, including circulatory system development; dichotomous subdivision of terminal units involved in salivary gland branching; and positive regulation of protein binding activity. Located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

PLXND1 Gene-Disease associations (from GenCC):

congenital heart defects, multiple types, 9
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Mobius syndrome
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P
persistent truncus arteriosus
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PLXND1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015977621).

BP6

Variant 3-129585954-G-A is Benign according to our data. Variant chr3-129585954-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056786.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXND1	NM_015103.3 link	c.1849C>T	p.Pro617Ser	missense_variant, splice_region_variant	Exon 5 of 36	ENST00000324093.9	NP_055918.3	Q9Y4D7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLXND1	ENST00000324093.9 link	c.1849C>T	p.Pro617Ser	missense_variant, splice_region_variant	Exon 5 of 36	1	NM_015103.3	ENSP00000317128.4	Q9Y4D7-1
PLXND1	ENST00000505237.2 link	c.505C>T	p.Pro169Ser	missense_variant, splice_region_variant	Exon 4 of 4	5		ENSP00000426241.2	H0YA64
PLXND1	ENST00000505665.5 link	n.325C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000423832.1	H0Y9D1

Frequencies

GnomAD3 genomes

AF:

0.0488

AC:

7427

AN:

152202

Hom.:

264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0364

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0830

Gnomad FIN

AF:

0.0346

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0549

GnomAD2 exomes

AF:

0.0512

AC:

12874

AN:

251336

AF XY:

0.0525

show subpopulations

Gnomad AFR exome

AF:

0.0679

Gnomad AMR exome

AF:

0.0272

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0320

Gnomad OTH exome

AF:

0.0556

GnomAD4 exome

AF:

0.0379

AC:

55342

AN:

1461650

Hom.:

1594

Cov.:

AF XY:

0.0395

AC XY:

28755

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.0722

AC:

2416

AN:

33478

American (AMR)

AF:

0.0281

AC:

1258

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3496

AN:

26134

East Asian (EAS)

AF:

0.121

AC:

4811

AN:

39700

South Asian (SAS)

AF:

0.0816

AC:

7038

AN:

86236

European-Finnish (FIN)

AF:

0.0366

AC:

1952

AN:

53264

Middle Eastern (MID)

AF:

0.0881

AC:

508

AN:

5766

European-Non Finnish (NFE)

AF:

0.0276

AC:

30742

AN:

1111960

Other (OTH)

AF:

0.0517

AC:

3121

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3120

6240

9360

12480

15600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1310

2620

3930

5240

6550

<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:

0.0488

AC:

7438

AN:

152320

Hom.:

263

Cov.:

AF XY:

0.0502

AC XY:

3741

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0680

AC:

2825

AN:

41570

American (AMR)

AF:

0.0363

AC:

556

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

459

AN:

3470

East Asian (EAS)

AF:

0.117

AC:

607

AN:

5188

South Asian (SAS)

AF:

0.0831

AC:

401

AN:

4826

European-Finnish (FIN)

AF:

0.0346

AC:

367

AN:

10618

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0306

AC:

2081

AN:

68022

Other (OTH)

AF:

0.0562

AC:

119

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

367

734

1100

1467

1834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0414

Hom.:

791

Bravo

AF:

0.0496

TwinsUK

AF:

0.0286

AC:

106

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.0654

AC:

288

ESP6500EA

AF:

0.0340

AC:

292

ExAC

AF:

0.0513

AC:

6225

Asia WGS

AF:

0.107

AC:

371

AN:

3478

EpiCase

AF:

0.0352

EpiControl

AF:

0.0362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLXND1-related disorder

Benign:1

Sep 24, 2019

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

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.050

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.20

N;.

PhyloP100

1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.047

Sift

Benign

0.67

T;D

Sift4G

Benign

0.83

T;D

Polyphen

0.0

B;.

Vest4

0.042

MPC

0.29

ClinPred

0.0052

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

gMVP

0.41

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0064

dbscSNV1_RF

Benign

0.25

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over