10-20145851-T-C

Variant names:

• chr10-20145851-T-C
• rs4634985
• NM_032812.9:c.665-1933T>C

Variant summary

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

The NM_032812.9(PLXDC2):​c.665-1933T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,978 control chromosomes in the GnomAD database, including 32,575 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 0.62 (32575 hom., cov: 32)
• Consequence: PLXDC2 NM_032812.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.665-1933T>C		intron_variant	Intron 5 of 13	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.518-1933T>C		intron_variant	Intron 4 of 12		NP_001269665.1
PLXDC2	XM_011519750.3	c.665-1933T>C		intron_variant	Intron 5 of 13		XP_011518052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLXDC2	ENST00000377252.5	c.665-1933T>C		intron_variant	Intron 5 of 13	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.518-1933T>C		intron_variant	Intron 4 of 12	1		ENSP00000366450.3
PLXDC2	ENST00000377238.2	n.440-1933T>C		intron_variant	Intron 4 of 12	5

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93533 AN: 151862 Hom.: 32573 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.616 AC: 93561 AN: 151978 Hom.: 32575 Cov.: 32 AF XY: 0.612 AC XY: 45433 AN XY: 74276

African (AFR) AF: 0.272 AC: 11285 AN: 41442

American (AMR) AF: 0.708 AC: 10794 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2404 AN: 3472

East Asian (EAS) AF: 0.500 AC: 2573 AN: 5148

South Asian (SAS) AF: 0.593 AC: 2853 AN: 4808

European-Finnish (FIN) AF: 0.713 AC: 7534 AN: 10570

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.793 AC: 53907 AN: 67974

Other (OTH) AF: 0.633 AC: 1333 AN: 2106

Alfa AF: 0.668 Hom.: 9755

Bravo AF: 0.599

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.20
PhyloP100		-1.0
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: rs4634985; hg19: chr10-20434780;