3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGT
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_014159.7(SETD2):c.4918-50_4918-43del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 733,814 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.00080 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00070 ( 0 hom. )
Consequence
SETD2
NM_014159.7 intron
NM_014159.7 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.22
Genes affected
SETD2 (HGNC:18420): (SET domain containing 2, histone lysine methyltransferase) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000805 (114/141664) while in subpopulation AFR AF= 0.00185 (70/37878). AF 95% confidence interval is 0.0015. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 114 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.4918-50_4918-43del | intron_variant | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.4918-50_4918-43del | intron_variant | 5 | NM_014159.7 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000805 AC: 114AN: 141566Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.000703 AC: 416AN: 592150Hom.: 0 AF XY: 0.000669 AC XY: 211AN XY: 315534
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GnomAD4 genome AF: 0.000805 AC: 114AN: 141664Hom.: 0 Cov.: 0 AF XY: 0.000786 AC XY: 54AN XY: 68668
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BranchPoint Hunter
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at