Variant 10-20147885-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032812.9(PLXDC2):c.766A>T(p.Ile256Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLXDC2
NM_032812.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

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:

PLXDC2 (HGNC:):

PLXDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLXDC2	NM_032812.9 linkuse as main transcript	c.766A>T	p.Ile256Phe	missense_variant	6/14	ENST00000377252.5	NP_116201.7	Q6UX71-1
PLXDC2	NM_001282736.2 linkuse as main transcript	c.619A>T	p.Ile207Phe	missense_variant	5/13		NP_001269665.1	Q6UX71-2
PLXDC2	XM_011519750.3 linkuse as main transcript	c.766A>T	p.Ile256Phe	missense_variant	6/14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLXDC2	ENST00000377252.5 linkuse as main transcript	c.766A>T	p.Ile256Phe	missense_variant	6/14	1	NM_032812.9	ENSP00000366460.3	Q6UX71-1
PLXDC2	ENST00000377242.7 linkuse as main transcript	c.619A>T	p.Ile207Phe	missense_variant	5/13	1		ENSP00000366450.3	Q6UX71-2
PLXDC2	ENST00000377238.2 linkuse as main transcript	n.541A>T		non_coding_transcript_exon_variant	5/13	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722784

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Aug 10, 2024

The c.766A>T (p.I256F) alteration is located in exon 6 (coding exon 6) of the PLXDC2 gene. This alteration results from a A to T substitution at nucleotide position 766, causing the isoleucine (I) at amino acid position 256 to be replaced by a phenylalanine (F). 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

0.33

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;T

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.8

.;L

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.94

P;P

Vest4

0.63

MutPred

0.38

.;Loss of methylation at K260 (P = 0.1074);

MVP

0.22

MPC

1.8

ClinPred

0.99

GERP RS

4.8

Varity_R

0.58

gMVP

0.67

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