rs144825663
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_014159.7(SETD2):c.5271C>T(p.Leu1757=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00537 in 1,611,750 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0038 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0055 ( 33 hom. )
Consequence
SETD2
NM_014159.7 synonymous
NM_014159.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.323
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 3-47088119-G-A is Benign according to our data. Variant chr3-47088119-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-47088119-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.323 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0038 (578/152256) while in subpopulation NFE AF= 0.00653 (444/68026). AF 95% confidence interval is 0.00603. There are 7 homozygotes in gnomad4. There are 262 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 578 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETD2 | NM_014159.7 | c.5271C>T | p.Leu1757= | synonymous_variant | 10/21 | ENST00000409792.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETD2 | ENST00000409792.4 | c.5271C>T | p.Leu1757= | synonymous_variant | 10/21 | 5 | NM_014159.7 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00380 AC: 578AN: 152138Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00327 AC: 814AN: 249006Hom.: 3 AF XY: 0.00314 AC XY: 422AN XY: 134578
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GnomAD4 exome AF: 0.00553 AC: 8077AN: 1459494Hom.: 33 Cov.: 31 AF XY: 0.00536 AC XY: 3889AN XY: 726012
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GnomAD4 genome ? AF: 0.00380 AC: 578AN: 152256Hom.: 7 Cov.: 32 AF XY: 0.00352 AC XY: 262AN XY: 74444
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Luscan-Lumish syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 30, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SETD2: BP4, BP7, BS2 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at