10-19817084-C-T

Variant names:

• chr10-19817084-C-T
• rs538990155
• NM_032812.9:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032812.9(PLXDC2):​c.5C>T​(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,397,598 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• 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]

ENSG00000285852 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5	c.5C>T	p.Ala2Val	missense_variant	Exon 1 of 14	1	NM_032812.9	ENSP00000366460.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397598 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689782

African (AFR) AF: 0.00 AC: 0 AN: 31600

American (AMR) AF: 0.00 AC: 0 AN: 36160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35798

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5246

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079060

Other (OTH) AF: 0.00 AC: 0 AN: 57962

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0092	.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.25	T;T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		3.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.49
MutPred		0.30		Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);
MVP		0.082
MPC		0.54
ClinPred		0.98	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.41
Mutation Taster		=87/13	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: rs538990155; hg19: chr10-20106013;