rs138761663

Variant names:

• chr10-20001906-G-A
• rs138761663
• NM_032812.9:c.244G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_032812.9(PLXDC2):​c.244G>A​(p.Val82Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000437 in 1,613,610 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (2 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.985
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00476259).
• BP6: Variant 10-20001906-G-A is Benign according to our data. Variant chr10-20001906-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 716202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.244G>A	p.Val82Ile	missense_variant	Exon 2 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.244G>A	p.Val82Ile	missense_variant	Exon 2 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.244G>A	p.Val82Ile	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.244G>A	p.Val82Ile	missense_variant	Exon 2 of 14	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.244G>A	p.Val82Ile	missense_variant	Exon 2 of 13	1		ENSP00000366450.3
ENSG00000307266	ENST00000824825.1	n.134+3632C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 342 AN: 152130 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.000582 AC: 146 AN: 250844 AF XY: 0.000465

Gnomad AFR exome AF: 0.00831

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000248 AC: 362 AN: 1461362 Hom.: 2 Cov.: 31 AF XY: 0.000212 AC XY: 154 AN XY: 726968

African (AFR) AF: 0.00894 AC: 299 AN: 33462

American (AMR) AF: 0.000313 AC: 14 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5452

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111954

Other (OTH) AF: 0.000497 AC: 30 AN: 60350

GnomAD4 genome AF: 0.00225 AC: 343 AN: 152248 Hom.: 1 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74420

African (AFR) AF: 0.00799 AC: 332 AN: 41546

American (AMR) AF: 0.000458 AC: 7 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000910 Hom.: 0

Bravo AF: 0.00275

ESP6500AA AF: 0.00840 AC: 37

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000717 AC: 87

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.045
DANN	Benign	0.81
DEOGEN2	Benign	0.0048	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;N
PhyloP100		-0.98
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.13
Sift	Benign	0.30	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.17	B;B
Vest4		0.24
MVP		0.068
MPC		0.091
ClinPred		0.015	T
GERP RS		-12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.013
gMVP		0.11
Mutation Taster		=94/6	polymorphism

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: rs138761663; hg19: chr10-20290835; COSMIC: COSV65918692;