10-19990229-A-G

Variant names:

• chr10-19990229-A-G
• rs16919668
• NM_032812.9:c.113-11546A>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.113-11546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,144 control chromosomes in the GnomAD database, including 4,027 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 0.21 (4027 hom., cov: 32)
• Consequence: PLXDC2 NM_032812.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.113-11546A>G		intron_variant	Intron 1 of 13	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.113-11546A>G		intron_variant	Intron 1 of 12		NP_001269665.1
PLXDC2	XM_011519750.3	c.113-11546A>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.113-11546A>G		intron_variant	Intron 1 of 13	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.113-11546A>G		intron_variant	Intron 1 of 12	1		ENSP00000366450.3
ENSG00000307266	ENST00000824825.1	n.135-4169T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32153 AN: 152026 Hom.: 4025 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.212 AC: 32191 AN: 152144 Hom.: 4027 Cov.: 32 AF XY: 0.208 AC XY: 15486 AN XY: 74400

African (AFR) AF: 0.355 AC: 14717 AN: 41474

American (AMR) AF: 0.130 AC: 1993 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3470

East Asian (EAS) AF: 0.149 AC: 769 AN: 5174

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1465 AN: 10588

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10919 AN: 68014

Other (OTH) AF: 0.188 AC: 397 AN: 2112

Alfa AF: 0.168 Hom.: 2442

Bravo AF: 0.217

Asia WGS AF: 0.194 AC: 677 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.63
PhyloP100		-0.34
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: rs16919668; hg19: chr10-20279158;