rs112285834
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004431.5(EPHA2):c.2352C>T(p.Thr784=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,613,926 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 19 hom., cov: 32)
Exomes 𝑓: 0.014 ( 192 hom. )
Consequence
EPHA2
NM_004431.5 synonymous
NM_004431.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.61
Genes affected
EPHA2 (HGNC:3386): (EPH receptor A2) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 1-16131844-G-A is Benign according to our data. Variant chr1-16131844-G-A is described in ClinVar as [Benign]. Clinvar id is 259390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.61 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1869/152308) while in subpopulation NFE AF= 0.0182 (1241/68018). AF 95% confidence interval is 0.0174. There are 19 homozygotes in gnomad4. There are 949 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1869 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EPHA2 | NM_004431.5 | c.2352C>T | p.Thr784= | synonymous_variant | 14/17 | ENST00000358432.8 | NP_004422.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPHA2 | ENST00000358432.8 | c.2352C>T | p.Thr784= | synonymous_variant | 14/17 | 1 | NM_004431.5 | ENSP00000351209 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0123 AC: 1866AN: 152190Hom.: 18 Cov.: 32
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GnomAD3 exomes AF: 0.0113 AC: 2824AN: 250352Hom.: 42 AF XY: 0.0109 AC XY: 1483AN XY: 135546
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GnomAD4 exome AF: 0.0137 AC: 20083AN: 1461618Hom.: 192 Cov.: 33 AF XY: 0.0135 AC XY: 9803AN XY: 727078
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GnomAD4 genome AF: 0.0123 AC: 1869AN: 152308Hom.: 19 Cov.: 32 AF XY: 0.0127 AC XY: 949AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cataract 6 multiple types Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2024 | - - |
Benign, 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 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 27, 2020 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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