14-74245180-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_182894.3(VSX2):c.471C>T(p.Ser157Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,612,744 control chromosomes in the GnomAD database, including 194,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S157S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.38 ( 13854 hom., cov: 27)

Exomes 𝑓: 0.49 ( 181047 hom. )

Consequence

VSX2
NM_182894.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.399

Publications

14 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), PanelApp Australia
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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 14-74245180-C-T is Benign according to our data. Variant chr14-74245180-C-T is described in ClinVar as Benign. ClinVar VariationId is 167840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSX2	NM_182894.3 link	c.471C>T	p.Ser157Ser	synonymous_variant	Exon 3 of 5	ENST00000261980.3	NP_878314.1	P58304

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSX2	ENST00000261980.3 link	c.471C>T	p.Ser157Ser	synonymous_variant	Exon 3 of 5	1	NM_182894.3	ENSP00000261980.2		P58304

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

57787

AN:

151214

Hom.:

13850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.0692

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.587

Gnomad MID

AF:

0.296

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.370

GnomAD2 exomes

AF:

0.429

AC:

107675

AN:

250814

AF XY:

0.431

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.392

Gnomad EAS exome

AF:

0.0530

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.442

GnomAD4 exome

AF:

0.485

AC:

708830

AN:

1461412

Hom.:

181047

Cov.:

AF XY:

0.482

AC XY:

350037

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.0986

AC:

3300

AN:

33470

American (AMR)

AF:

0.496

AC:

22164

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

10243

AN:

26126

East Asian (EAS)

AF:

0.0879

AC:

3491

AN:

39694

South Asian (SAS)

AF:

0.344

AC:

29670

AN:

86240

European-Finnish (FIN)

AF:

0.570

AC:

30378

AN:

53336

Middle Eastern (MID)

AF:

0.307

AC:

1771

AN:

5766

European-Non Finnish (NFE)

AF:

0.523

AC:

581058

AN:

1111726

Other (OTH)

AF:

0.443

AC:

26755

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

20686

41371

62057

82742

103428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16248

32496

48744

64992

81240

<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:

0.382

AC:

57803

AN:

151332

Hom.:

13854

Cov.:

AF XY:

0.385

AC XY:

28473

AN XY:

73872

show subpopulations

African (AFR)

AF:

0.117

AC:

4821

AN:

41292

American (AMR)

AF:

0.454

AC:

6904

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3464

East Asian (EAS)

AF:

0.0694

AC:

357

AN:

5144

South Asian (SAS)

AF:

0.317

AC:

1508

AN:

4754

European-Finnish (FIN)

AF:

0.587

AC:

6148

AN:

10474

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.521

AC:

35262

AN:

67702

Other (OTH)

AF:

0.371

AC:

777

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1453

2907

4360

5814

7267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.455

Hom.:

8804

Bravo

AF:

0.360

Asia WGS

AF:

0.219

AC:

761

AN:

3478

EpiCase

AF:

0.495

EpiControl

AF:

0.497

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 27, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Isolated microphthalmia 2

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microphthalmia, isolated, with coloboma 3

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microphthalmia

Benign:1

Nov 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.40

Mutation Taster

=81/19

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over