NM_032812.9:c.282C>A

Variant names:

• chr10-20001944-C-A
• rs763045853
• NM_032812.9:c.282C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032812.9(PLXDC2):​c.282C>A​(p.Asp94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 0 publications found

Genes affected

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

ENSG00000307266 (HGNC:):

ACMG classification

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=0.33381128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.282C>A	p.Asp94Glu	missense_variant	Exon 2 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.282C>A	p.Asp94Glu	missense_variant	Exon 2 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.282C>A	p.Asp94Glu	missense_variant	Exon 2 of 14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5	c.282C>A	p.Asp94Glu	missense_variant	Exon 2 of 14	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.282C>A	p.Asp94Glu	missense_variant	Exon 2 of 13	1		ENSP00000366450.3
ENSG00000307266	ENST00000824825.1	n.134+3594G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460742 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726688

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4962

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111924

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		-0.087
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.74	N;N
REVEL	Benign	0.20
Sift	Benign	0.19	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.99	D;B
Vest4		0.67
MutPred		0.44		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.11
MPC		0.12
ClinPred		0.68	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.47
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs763045853; hg19: chr10-20290873;