rs1367212508

Variant names:

• chr10-20001979-A-G
• rs1367212508
• NM_032812.9:c.317A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032812.9(PLXDC2):​c.317A>G​(p.Gln106Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,611,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25085762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.317A>G	p.Gln106Arg	missense_variant	Exon 2 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.317A>G	p.Gln106Arg	missense_variant	Exon 2 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.317A>G	p.Gln106Arg	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.317A>G	p.Gln106Arg	missense_variant	Exon 2 of 14	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.317A>G	p.Gln106Arg	missense_variant	Exon 2 of 13	1		ENSP00000366450.3
ENSG00000307266	ENST00000824825.1	n.134+3559T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248198 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458972 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 725656

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 85976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4328

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111458

Other (OTH) AF: 0.00 AC: 0 AN: 60202

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317A>G (p.Q106R) alteration is located in exon 2 (coding exon 2) of the PLXDC2 gene. This alteration results from a A to G substitution at nucleotide position 317, causing the glutamine (Q) at amino acid position 106 to be replaced by an arginine (R). 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	0.080
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	0.043
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L
PhyloP100		6.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.19
Sift	Benign	0.069	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.49	P;B
Vest4		0.59
MutPred		0.27		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.24
MPC		0.16
ClinPred		0.33	T
GERP RS		5.8
Varity_R		0.075
gMVP		0.76
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1367212508; hg19: chr10-20290908;