10-20147867-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032812.9(PLXDC2):c.748C>A(p.Leu250Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90

Genes affected

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

ACMG classification

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=0.15498549).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXDC2	NM_032812.9	c.748C>A	p.Leu250Ile	missense_variant	6/14	ENST00000377252.5
PLXDC2	NM_001282736.2	c.601C>A	p.Leu201Ile	missense_variant	5/13
PLXDC2	XM_011519750.3	c.748C>A	p.Leu250Ile	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXDC2	ENST00000377252.5	c.748C>A	p.Leu250Ile	missense_variant	6/14	1	NM_032812.9	P1
PLXDC2	ENST00000377242.7	c.601C>A	p.Leu201Ile	missense_variant	5/13	1
PLXDC2	ENST00000377238.2	n.523C>A		non_coding_transcript_exon_variant	5/13	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459054 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726026

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.748C>A (p.L250I) alteration is located in exon 6 (coding exon 6) of the PLXDC2 gene. This alteration results from a C to A substitution at nucleotide position 748, causing the leucine (L) at amino acid position 250 to be replaced by an isoleucine (I). 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	0.19
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	23
Dann	Benign	0.97
Eigen	Benign	-0.16
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.74	T
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.16
Sift	Benign	0.40	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.013	B;B
Vest4		0.34
MutPred		0.52		.;Gain of sheet (P = 0.0827);
MVP		0.15
MPC		0.87
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-20436796;