Genetic Variant PLXDC2:p.Glu108Gln (chr10-20001984-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032812.9(PLXDC2):c.322G>C(p.Glu108Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000686 in 1,458,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E108K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PLXDC2
NM_032812.9 missense, splice_region

Scores

Splicing: ADA: 0.8784

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.50

Publications

0 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:

ENSG00000307266 (HGNC:):

ENSG00000307266 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41707474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9 link	c.322G>C	p.Glu108Gln	missense_variant, splice_region_variant	Exon 2 of 14	ENST00000377252.5	NP_116201.7	Q6UX71-1
PLXDC2	NM_001282736.2 link	c.322G>C	p.Glu108Gln	missense_variant, splice_region_variant	Exon 2 of 13		NP_001269665.1	Q6UX71-2
PLXDC2	XM_011519750.3 link	c.322G>C	p.Glu108Gln	missense_variant, splice_region_variant	Exon 2 of 14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLXDC2	ENST00000377252.5 link	c.322G>C	p.Glu108Gln	missense_variant, splice_region_variant	Exon 2 of 14	1	NM_032812.9	ENSP00000366460.3	Q6UX71-1
PLXDC2	ENST00000377242.7 link	c.322G>C	p.Glu108Gln	missense_variant, splice_region_variant	Exon 2 of 13	1		ENSP00000366450.3	Q6UX71-2
ENSG00000307266	ENST00000824825.1 link	n.134+3554C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458758

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725506

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4322

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111362

Other (OTH)

AF:

0.00

AC:

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

.;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M

PhyloP100

6.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.27

Sift

Benign

0.10

T;T

Sift4G

Benign

0.51

T;T

Polyphen

1.0

D;B

Vest4

0.76

MutPred

0.28

Loss of disorder (P = 0.2467);Loss of disorder (P = 0.2467);

MVP

0.16

MPC

0.23

ClinPred

0.85

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.56

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.88

dbscSNV1_RF

Benign

0.65

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over