dbSNP rs3817405: PLXDC2:p.Val396Ile (chr10-20217489-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_032812.9(PLXDC2):c.1186G>A(p.Val396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 1,611,310 control chromosomes in the GnomAD database, including 350,891 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 32623 hom., cov: 29)

Exomes 𝑓: 0.66 ( 318268 hom. )

Consequence

PLXDC2
NM_032812.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.54

Publications

36 publications found

Variant links:

Genes affected

PLXDC2 (HGNC:21013): (plexin domain containing 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLXDC2 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 (MetaRNN=1.3601372E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9 link	c.1186G>A	p.Val396Ile	missense_variant	Exon 11 of 14	ENST00000377252.5	NP_116201.7	Q6UX71-1
PLXDC2	NM_001282736.2 link	c.1039G>A	p.Val347Ile	missense_variant	Exon 10 of 13		NP_001269665.1	Q6UX71-2
PLXDC2	XM_011519750.3 link	c.1186G>A	p.Val396Ile	missense_variant	Exon 11 of 14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLXDC2	ENST00000377252.5 link	c.1186G>A	p.Val396Ile	missense_variant	Exon 11 of 14	1	NM_032812.9	ENSP00000366460.3	Q6UX71-1
PLXDC2	ENST00000377242.7 link	c.1039G>A	p.Val347Ile	missense_variant	Exon 10 of 13	1		ENSP00000366450.3	Q6UX71-2
PLXDC2	ENST00000377238.2 link	n.961G>A		non_coding_transcript_exon_variant	Exon 10 of 13	5

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98581

AN:

151460

Hom.:

32588

Cov.:

show subpopulations

Gnomad AFR

AF:

0.697

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.619

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.676

GnomAD2 exomes

AF:

0.603

AC:

151147

AN:

250538

AF XY:

0.615

show subpopulations

Gnomad AFR exome

AF:

0.700

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.751

Gnomad EAS exome

AF:

0.290

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.678

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.656

AC:

956889

AN:

1459734

Hom.:

318268

Cov.:

AF XY:

0.657

AC XY:

476920

AN XY:

726224

show subpopulations

African (AFR)

AF:

0.699

AC:

23362

AN:

33402

American (AMR)

AF:

0.409

AC:

18240

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.751

AC:

19577

AN:

26082

East Asian (EAS)

AF:

0.357

AC:

14128

AN:

39602

South Asian (SAS)

AF:

0.635

AC:

54664

AN:

86046

European-Finnish (FIN)

AF:

0.615

AC:

32779

AN:

53336

Middle Eastern (MID)

AF:

0.791

AC:

4554

AN:

5760

European-Non Finnish (NFE)

AF:

0.675

AC:

749884

AN:

1110632

Other (OTH)

AF:

0.659

AC:

39701

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16473

32946

49420

65893

82366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19158

38316

57474

76632

95790

<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:

0.651

AC:

98666

AN:

151576

Hom.:

32623

Cov.:

AF XY:

0.644

AC XY:

47682

AN XY:

74010

show subpopulations

African (AFR)

AF:

0.698

AC:

28833

AN:

41322

American (AMR)

AF:

0.536

AC:

8149

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

2603

AN:

3470

East Asian (EAS)

AF:

0.305

AC:

1555

AN:

5104

South Asian (SAS)

AF:

0.608

AC:

2922

AN:

4804

European-Finnish (FIN)

AF:

0.619

AC:

6465

AN:

10442

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.675

AC:

45867

AN:

67912

Other (OTH)

AF:

0.680

AC:

1436

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1691

3382

5072

6763

8454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.669

Hom.:

129138

Bravo

AF:

0.645

TwinsUK

AF:

0.666

AC:

2471

ALSPAC

AF:

0.657

AC:

2534

ESP6500AA

AF:

0.692

AC:

3050

ESP6500EA

AF:

0.686

AC:

5903

ExAC

AF:

0.615

AC:

74674

Asia WGS

AF:

0.499

AC:

1734

AN:

3476

EpiCase

AF:

0.694

EpiControl

AF:

0.700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0010

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0075

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.082

T;T

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

PhyloP100

-1.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.20

Sift

Benign

0.44

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0030

B;B

Vest4

0.065

MPC

0.015

ClinPred

0.019

GERP RS

-11

Varity_R

0.018

gMVP

0.17

Mutation Taster

=97/3

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