chr10-20001883-C-T

Variant names:

• chr10-20001883-C-T
• rs115833666
• NM_032812.9:c.221C>T

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.221C>T​(p.Ala74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000807 in 1,613,900 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (3 hom.)
• Consequence: PLXDC2 NM_032812.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.97
• 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041987896).
• BP6: Variant 10-20001883-C-T is Benign according to our data. Variant chr10-20001883-C-T is described in ClinVar as [Benign]. Clinvar id is 712486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLXDC2	NM_032812.9	c.221C>T	p.Ala74Val	missense_variant	Exon 2 of 14	ENST00000377252.5	NP_116201.7
PLXDC2	NM_001282736.2	c.221C>T	p.Ala74Val	missense_variant	Exon 2 of 13		NP_001269665.1
PLXDC2	XM_011519750.3	c.221C>T	p.Ala74Val	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.221C>T	p.Ala74Val	missense_variant	Exon 2 of 14	1	NM_032812.9	ENSP00000366460.3
PLXDC2	ENST00000377242.7	c.221C>T	p.Ala74Val	missense_variant	Exon 2 of 13	1		ENSP00000366450.3
ENSG00000307266	ENST00000824825.1	n.134+3655G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00431 AC: 655 AN: 152116 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00119 AC: 298 AN: 250868 AF XY: 0.000863

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.000898

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.000441 AC: 645 AN: 1461666 Hom.: 3 Cov.: 31 AF XY: 0.000382 AC XY: 278 AN XY: 727114

African (AFR) AF: 0.0145 AC: 485 AN: 33474

American (AMR) AF: 0.00110 AC: 49 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000529 AC: 3 AN: 5668

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111966

Other (OTH) AF: 0.00129 AC: 78 AN: 60368

GnomAD4 genome AF: 0.00432 AC: 657 AN: 152234 Hom.: 5 Cov.: 32 AF XY: 0.00406 AC XY: 302 AN XY: 74432

African (AFR) AF: 0.0147 AC: 611 AN: 41526

American (AMR) AF: 0.00209 AC: 32 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68022

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00163 Hom.: 2

Bravo AF: 0.00528

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0145 AC: 64

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00143 AC: 174

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.0042	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.090	N;N
PhyloP100		2.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.64	N;N
REVEL	Benign	0.063
Sift	Uncertain	0.027	D;T
Sift4G	Benign	0.29	T;T
Polyphen		0.55	P;B
Vest4		0.30
MVP		0.068
MPC		0.11
ClinPred		0.012	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.20
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs115833666; hg19: chr10-20290812; COSMIC: COSV101024301;