NM_032812.9:c.122A>T

Variant names:

• chr10-20001784-A-T
• NM_032812.9:c.122A>T

Variant summary

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

The NM_032812.9(PLXDC2):​c.122A>T​(p.Tyr41Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 14/22 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)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06
• 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 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.122A>T	p.Tyr41Phe	missense_variant	Exon 2 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.122A>T	p.Tyr41Phe	missense_variant	Exon 2 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.122A>T	p.Tyr41Phe	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.122A>T	p.Tyr41Phe	missense_variant	Exon 2 of 14	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.122A>T	p.Tyr41Phe	missense_variant	Exon 2 of 13	1		ENSP00000366450.3
ENSG00000307266	ENST00000824825.1	n.134+3754T>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.122A>T (p.Y41F) alteration is located in exon 2 (coding exon 2) of the PLXDC2 gene. This alteration results from a A to T substitution at nucleotide position 122, causing the tyrosine (Y) at amino acid position 41 to be replaced by a phenylalanine (F). 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	0.099
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.025	.;T
Eigen	Benign	0.051
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		6.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.79	P;P
Vest4		0.60
MutPred		0.62		Loss of phosphorylation at Y41 (P = 0.0423);Loss of phosphorylation at Y41 (P = 0.0423);
MVP		0.12
MPC		0.15
ClinPred		0.84	D
GERP RS		5.9
Varity_R		0.086
gMVP		0.41
Mutation Taster		=88/12	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

hg19: chr10-20290713;