rs78509400
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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.Asp174Asp) 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
NM_182894.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.819
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]
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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. Median coverage is 29. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VSX2 | NM_182894.3 | c.522C>T | p.Asp174Asp | synonymous_variant | 3/5 | ENST00000261980.3 | NP_878314.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VSX2 | ENST00000261980.3 | c.522C>T | p.Asp174Asp | synonymous_variant | 3/5 | 1 | NM_182894.3 | ENSP00000261980.2 |
Frequencies
GnomAD3 genomes AF: 0.00254 AC: 386AN: 151734Hom.: 4 Cov.: 29
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GnomAD3 exomes AF: 0.000656 AC: 165AN: 251400Hom.: 1 AF XY: 0.000530 AC XY: 72AN XY: 135894
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GnomAD4 exome AF: 0.000244 AC: 357AN: 1461854Hom.: 2 Cov.: 34 AF XY: 0.000227 AC XY: 165AN XY: 727230
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GnomAD4 genome AF: 0.00254 AC: 386AN: 151852Hom.: 4 Cov.: 29 AF XY: 0.00226 AC XY: 168AN XY: 74212
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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
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 02, 2016 | - - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
VSX2-related disorder Benign:1
Benign, no assertion criteria provided | 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). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at