Variant 10-19817087-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032812.9(PLXDC2):c.8G>A(p.Arg3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,400,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

PLXDC2
NM_032812.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1709567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLXDC2	NM_032812.9 linkuse as main transcript	c.8G>A	p.Arg3Lys	missense_variant	1/14	ENST00000377252.5
PLXDC2	NM_001282736.2 linkuse as main transcript	c.8G>A	p.Arg3Lys	missense_variant	1/13
PLXDC2	XM_011519750.3 linkuse as main transcript	c.8G>A	p.Arg3Lys	missense_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXDC2	ENST00000377252.5 linkuse as main transcript	c.8G>A	p.Arg3Lys	missense_variant	1/14	1	NM_032812.9	P1	Q6UX71-1
PLXDC2	ENST00000377242.7 linkuse as main transcript	c.8G>A	p.Arg3Lys	missense_variant	1/13	1			Q6UX71-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000314

AC:

AN:

158998

Hom.:

AF XY:

0.0000356

AC XY:

AN XY:

84256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000392

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:

0.0000640

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000250

AC:

AN:

1400048

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

691074

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000549

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000259

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000516

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000928

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

Jun 07, 2023

The c.8G>A (p.R3K) alteration is located in exon 1 (coding exon 1) of the PLXDC2 gene. This alteration results from a G to A substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.32

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.90

P;P

Vest4

0.14

MVP

0.15

MPC

0.12

ClinPred

0.28

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.39

gMVP

0.27

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