rs78509400

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_182894.3(VSX2):c.522C>T(p.Asp174=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,613,706 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 29)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

VSX2
NM_182894.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.819

Variant links:

Genes affected

VSX2 (HGNC:1975): (visual system homeobox 2) This gene encodes a homeobox protein originally described as a retina-specific transcription factor. Mutations in this gene are associated with microphthalmia, cataracts and iris abnormalities. [provided by RefSeq, Oct 2009]

VSX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 14-74245231-C-T is Benign according to our data. Variant chr14-74245231-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 289848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.819 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00254 (386/151852) while in subpopulation AFR AF= 0.00877 (363/41376). AF 95% confidence interval is 0.00803. There are 4 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSX2	NM_182894.3 linkuse as main transcript	c.522C>T	p.Asp174=	synonymous_variant	3/5	ENST00000261980.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX2	ENST00000261980.3 linkuse as main transcript	c.522C>T	p.Asp174=	synonymous_variant	3/5	1	NM_182894.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00880

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

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:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000656

AC:

165

AN:

251400

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00966

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000244

AC:

357

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

165

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00917

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.00254

AC:

386

AN:

151852

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.00877

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00290

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 02, 2016

- -

VSX2-related condition

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 14, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Microphthalmia

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Dec 14, 2019

- -

Isolated microphthalmia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

Cadd

Benign

8.2

Dann

Benign

0.67

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