10-20046870-A-T

Variant names:

• chr10-20046870-A-T
• rs1835806907
• NM_032812.9:c.326A>T

Variant summary

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

The NM_032812.9(PLXDC2):​c.326A>T​(p.Glu109Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,176 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLXDC2 NM_032812.9 missense, splice_region
• Scores: Splicing: ADA: 0.6537
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.94
• 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]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032812.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXDC2	NM_032812.9	MANE Select	c.326A>T	p.Glu109Val	missense splice_region	Exon 3 of 14	NP_116201.7
	PLXDC2	NM_001282736.2		c.325-21300A>T		intron	N/A	NP_001269665.1	Q6UX71-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLXDC2	ENST00000377252.5	TSL:1 MANE Select	c.326A>T	p.Glu109Val	missense splice_region	Exon 3 of 14	ENSP00000366460.3	Q6UX71-1
	PLXDC2	ENST00000377242.7	TSL:1	c.325-21300A>T		intron	N/A	ENSP00000366450.3	Q6UX71-2
	PLXDC2	ENST00000888733.1		c.326A>T	p.Glu109Val	missense splice_region	Exon 3 of 15	ENSP00000558792.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451176 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721852

African (AFR) AF: 0.0000304 AC: 1 AN: 32948

American (AMR) AF: 0.00 AC: 0 AN: 42148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25582

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.00 AC: 0 AN: 84102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108154

Other (OTH) AF: 0.00 AC: 0 AN: 59920

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.26
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.013	D
Polyphen		0.24	B
Vest4		0.84
MutPred		0.36		Loss of disorder (P = 0.023)
MVP		0.22
MPC		0.20
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.67
Mutation Taster		=48/52	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.65
dbscSNV1_RF	Pathogenic	0.78
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: rs1835806907; hg19: chr10-20335799;