rs746404627
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBS1_Supporting
The NM_014159.7(SETD2):c.6614A>G(p.His2205Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,614,022 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
NM_014159.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.6614A>G | p.His2205Arg | missense_variant | 15/21 | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.6614A>G | p.His2205Arg | missense_variant | 15/21 | 5 | NM_014159.7 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251070Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135704
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727202
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
Luscan-Lumish syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2022 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 475533). This variant has not been reported in the literature in individuals affected with SETD2-related conditions. This variant is present in population databases (rs746404627, gnomAD 0.006%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2205 of the SETD2 protein (p.His2205Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at