rs10508593

Variant names:

• chr10-19852780-A-G
• rs10508593
• NM_032812.9:c.112+35589A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032812.9(PLXDC2):​c.112+35589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 152,276 control chromosomes in the GnomAD database, including 643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.067 (643 hom., cov: 33)
• Consequence: PLXDC2 NM_032812.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.112+35589A>G		intron_variant	Intron 1 of 13	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.112+35589A>G		intron_variant	Intron 1 of 12		NP_001269665.1
PLXDC2	XM_011519750.3	c.112+35589A>G		intron_variant	Intron 1 of 13		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5	c.112+35589A>G		intron_variant	Intron 1 of 13	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.112+35589A>G		intron_variant	Intron 1 of 12	1		ENSP00000366450.3

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10158 AN: 152158 Hom.: 643 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0293

Gnomad OTH AF: 0.0655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0669 AC: 10180 AN: 152276 Hom.: 643 Cov.: 33 AF XY: 0.0659 AC XY: 4904 AN XY: 74452

African (AFR) AF: 0.167 AC: 6946 AN: 41532

American (AMR) AF: 0.0370 AC: 566 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5182

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4826

European-Finnish (FIN) AF: 0.0106 AC: 113 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0293 AC: 1992 AN: 68024

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0385 Hom.: 534

Bravo AF: 0.0753

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.63
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs10508593; hg19: chr10-20141709;