rs61747367

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_182894.3(VSX2):c.162C>A(p.Asp54Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,549,210 control chromosomes in the GnomAD database, including 2 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D54D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

VSX2
NM_182894.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 1.12

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

isolated microphthalmia 2
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
microphthalmia, isolated, with coloboma 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
microphthalmia
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics
isolated anophthalmia-microphthalmia syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

VSX2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_182894.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0077951252).

BP6

Variant 14-74239723-C-A is Benign according to our data. Variant chr14-74239723-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 468358.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00241 (367/152316) while in subpopulation AFR AF = 0.00818 (340/41568). AF 95% confidence interval is 0.00746. There are 0 homozygotes in GnomAd4. There are 175 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182894.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSX2	NM_182894.3	MANE Select	c.162C>A	p.Asp54Glu	missense	Exon 1 of 5	NP_878314.1	P58304

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSX2	ENST00000261980.3	TSL:1 MANE Select	c.162C>A	p.Asp54Glu	missense	Exon 1 of 5	ENSP00000261980.2	P58304

Frequencies

GnomAD3 genomes

AF:

0.00241

AC:

367

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.00

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000570

AC:

AN:

145736

AF XY:

0.000432

show subpopulations

Gnomad AFR exome

AF:

0.00917

Gnomad AMR exome

AF:

0.000735

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000304

AC:

425

AN:

1396894

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

191

AN XY:

688882

show subpopulations

African (AFR)

AF:

0.0101

AC:

318

AN:

31590

American (AMR)

AF:

0.000729

AC:

AN:

35670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25148

East Asian (EAS)

AF:

0.000252

AC:

AN:

35766

South Asian (SAS)

AF:

0.0000631

AC:

AN:

79198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47808

Middle Eastern (MID)

AF:

0.000966

AC:

AN:

5176

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

1078648

Other (OTH)

AF:

0.000864

AC:

AN:

57890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00241

AC:

367

AN:

152316

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00818

AC:

340

AN:

41568

American (AMR)

AF:

0.00144

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.00273

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Isolated microphthalmia 2 (2)

Microphthalmia (1)

Microphthalmia, isolated, with coloboma 3 (1)

not provided (1)

VSX2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.61

MutationAssessor

Benign

-0.23

PhyloP100

1.1

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.070

REVEL

Benign

0.22

Sift

Benign

0.66

Sift4G

Benign

0.68

PromoterAI

0.017

Neutral

(source)

Varity_R

0.089

gMVP

0.30

Mutation Taster

=97/3

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over