rs61747367
Variant summary
Our verdict is Benign. Variant got -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. 13/20 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
Consequence
NM_182894.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VSX2 | NM_182894.3 | c.162C>A | p.Asp54Glu | missense_variant | 1/5 | ENST00000261980.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VSX2 | ENST00000261980.3 | c.162C>A | p.Asp54Glu | missense_variant | 1/5 | 1 | NM_182894.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00241 AC: 367AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000570 AC: 83AN: 145736Hom.: 1 AF XY: 0.000432 AC XY: 34AN XY: 78688
GnomAD4 exome AF: 0.000304 AC: 425AN: 1396894Hom.: 2 Cov.: 32 AF XY: 0.000277 AC XY: 191AN XY: 688882
GnomAD4 genome ? AF: 0.00241 AC: 367AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.00235 AC XY: 175AN XY: 74484
ClinVar
Submissions by phenotype
Isolated microphthalmia 2 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Microphthalmia, isolated, with coloboma 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Microphthalmia Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
VSX2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 23, 2019 | 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at