Variant 10-19817093-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032812.9(PLXDC2):c.14C>G(p.Pro5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000791 in 1,555,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

PLXDC2
NM_032812.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.444

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0223912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXDC2	NM_032812.9 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/14	ENST00000377252.5	NP_116201.7	Q6UX71-1
PLXDC2	NM_001282736.2 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/13		NP_001269665.1	Q6UX71-2
PLXDC2	XM_011519750.3 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/14	1	NM_032812.9	ENSP00000366460.3		Q6UX71-1
PLXDC2	ENST00000377242.7 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/13	1		ENSP00000366450.3		Q6UX71-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

163406

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

86786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000827

AC:

116

AN:

1403116

Hom.:

Cov.:

AF XY:

0.0000779

AC XY:

AN XY:

692800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000888

Gnomad4 OTH exome

AF:

0.000327

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000180

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.14C>G (p.P5R) alteration is located in exon 1 (coding exon 1) of the PLXDC2 gene. This alteration results from a C to G substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.021

.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.41

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.047

Sift

Benign

1.0

T;T

Sift4G

Benign

0.93

T;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.043

MPC

0.12

ClinPred

0.032

GERP RS

-3.0

Varity_R

0.085

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over