rs758978165
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000358432.8(EPHA2):c.1118C>T(p.Ser373Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
ENST00000358432.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EPHA2 | NM_004431.5 | c.1118C>T | p.Ser373Phe | missense_variant | 5/17 | ENST00000358432.8 | NP_004422.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EPHA2 | ENST00000358432.8 | c.1118C>T | p.Ser373Phe | missense_variant | 5/17 | 1 | NM_004431.5 | ENSP00000351209 | P1 | |
EPHA2 | ENST00000480202.1 | n.323C>T | non_coding_transcript_exon_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249678Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135180
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1460940Hom.: 0 Cov.: 32 AF XY: 0.0000303 AC XY: 22AN XY: 726806
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74388
ClinVar
Submissions by phenotype
Cataract 6 multiple types Uncertain:2
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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 19, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with EPHA2-related disease. This variant is present in population databases (rs758978165, ExAC 0.002%). This sequence change replaces serine with phenylalanine at codon 373 of the EPHA2 protein (p.Ser373Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 18, 2024 | The c.1118C>T (p.S373F) alteration is located in exon 5 (coding exon 5) of the EPHA2 gene. This alteration results from a C to T substitution at nucleotide position 1118, causing the serine (S) at amino acid position 373 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at