4-102885351-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001008388.5(CISD2):c.239C>T(p.Pro80Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P80P) has been classified as Likely benign.
Frequency
Consequence
NM_001008388.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CISD2 | NM_001008388.5 | c.239C>T | p.Pro80Leu | missense_variant | 2/3 | ENST00000273986.10 | |
SLC9B1 | NM_001100874.3 | c.1333-23G>A | intron_variant | ||||
SLC9B1 | NR_047513.2 | n.1313-23G>A | intron_variant, non_coding_transcript_variant | ||||
SLC9B1 | NR_047515.2 | n.1214-62G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CISD2 | ENST00000273986.10 | c.239C>T | p.Pro80Leu | missense_variant | 2/3 | 1 | NM_001008388.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152012Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251250Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135814
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461676Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727140
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152012Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74234
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 80 of the CISD2 protein (p.Pro80Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CISD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1448359). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. - |
Wolfram syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 18, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at