10-19817149-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032812.9(PLXDC2):c.70C>A(p.Gln24Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.912

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078793645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLXDC2	NM_032812.9	c.70C>A	p.Gln24Lys	missense_variant	1/14	ENST00000377252.5
PLXDC2	NM_001282736.2	c.70C>A	p.Gln24Lys	missense_variant	1/13
PLXDC2	XM_011519750.3	c.70C>A	p.Gln24Lys	missense_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLXDC2	ENST00000377252.5	c.70C>A	p.Gln24Lys	missense_variant	1/14	1	NM_032812.9	P1
PLXDC2	ENST00000377242.7	c.70C>A	p.Gln24Lys	missense_variant	1/13	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423992 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 704906

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.18e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.70C>A (p.Q24K) alteration is located in exon 1 (coding exon 1) of the PLXDC2 gene. This alteration results from a C to A substitution at nucleotide position 70, causing the glutamine (Q) at amino acid position 24 to be replaced by a lysine (K). 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	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	13
Dann	Benign	0.70
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.039
Sift	Benign	0.075	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.31		Gain of methylation at Q24 (P = 0.0062);Gain of methylation at Q24 (P = 0.0062);
MVP		0.068
MPC		0.14
ClinPred		0.063	T
GERP RS		2.6
Varity_R		0.073
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-20106078;