10-20143316-T-C

Variant names:

• chr10-20143316-T-C
• NM_032812.9:c.563T>C

Variant summary

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

The NM_032812.9(PLXDC2):​c.563T>C​(p.Val188Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98
• 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.563T>C	p.Val188Ala	missense_variant	Exon 5 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.416T>C	p.Val139Ala	missense_variant	Exon 4 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.563T>C	p.Val188Ala	missense_variant	Exon 5 of 14		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5	c.563T>C	p.Val188Ala	missense_variant	Exon 5 of 14	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.416T>C	p.Val139Ala	missense_variant	Exon 4 of 13	1		ENSP00000366450.3
PLXDC2	ENST00000377238.2	n.338T>C		non_coding_transcript_exon_variant	Exon 4 of 13	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.563T>C (p.V188A) alteration is located in exon 5 (coding exon 5) of the PLXDC2 gene. This alteration results from a T to C substitution at nucleotide position 563, causing the valine (V) at amino acid position 188 to be replaced by an alanine (A). 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	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	.;M
PhyloP100		8.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.48
Sift	Benign	0.097	T;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.30	B;B
Vest4		0.58
MutPred		0.38		.;Loss of sheet (P = 0.1158);
MVP		0.50
MPC		1.1
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.66
Mutation Taster		=40/60	disease causing

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

hg19: chr10-20432245;