Variant 14-74862615-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001243007.2(PROX2):c.1220A>G(p.Glu407Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,613,986 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 23 hom. )

Consequence

PROX2
NM_001243007.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

PROX2 (HGNC:26715): (prospero homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PROX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044588447).

BP6

Variant 14-74862615-T-C is Benign according to our data. Variant chr14-74862615-T-C is described in ClinVar as [Benign]. Clinvar id is 774334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PROX2	NM_001243007.2 linkuse as main transcript	c.1220A>G	p.Glu407Gly	missense_variant	3/6	ENST00000556489.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PROX2	ENST00000556489.4 linkuse as main transcript	c.1220A>G	p.Glu407Gly	missense_variant	3/6	1	NM_001243007.2	P1
PROX2	ENST00000673765.1 linkuse as main transcript	c.732+488A>G		intron_variant					Q3B8N5-2

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00369

AC:

920

AN:

249278

Hom.:

AF XY:

0.00365

AC XY:

494

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.000387

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.00501

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00408

AC:

5967

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

2940

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0142

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152290

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

260

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00431

Hom.:

Bravo

AF:

0.00223

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000245

AC:

ESP6500EA

AF:

0.00311

AC:

ExAC

AF:

0.00395

AC:

478

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00350

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	PROX2: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 03, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.082

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.033

Sift

Benign

0.27

Sift4G

Benign

0.28

Polyphen

0.099

Vest4

0.19

MVP

0.27

ClinPred

0.024

GERP RS

1.7

gMVP

0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over