rs11717033
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_014159.7(SETD2):c.72-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 927,100 control chromosomes in the GnomAD database, including 935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.030 ( 95 hom., cov: 32)
Exomes 𝑓: 0.042 ( 840 hom. )
Consequence
SETD2
NM_014159.7 intron
NM_014159.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.247
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 3-47126729-T-C is Benign according to our data. Variant chr3-47126729-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187337.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.72-66A>G | intron_variant | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.72-66A>G | intron_variant | 5 | NM_014159.7 | P3 | |||
SETD2 | ENST00000412450.1 | c.-61-66A>G | intron_variant | 2 | |||||
SETD2 | ENST00000638947.2 | c.-45-2181A>G | intron_variant | 5 | A2 | ||||
SETD2 | ENST00000691544.1 | c.72-28648A>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0303 AC: 4604AN: 152190Hom.: 96 Cov.: 32
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GnomAD4 exome AF: 0.0417 AC: 32304AN: 774792Hom.: 840 AF XY: 0.0424 AC XY: 17160AN XY: 404278
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GnomAD4 genome ? AF: 0.0302 AC: 4603AN: 152308Hom.: 95 Cov.: 32 AF XY: 0.0285 AC XY: 2124AN XY: 74492
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at