GeneBe

3-47062371-GTTTTTTT-GTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014159.7(SETD2):​c.6110-30_6110-26delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,219,822 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: not found (cov: 0)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Publications

0 publications found
Variant links:
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]
SETD2 Gene-Disease associations (from GenCC):
  • Luscan-Lumish syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • SETD2-related neurodevelopmental disorder without or with macrocephaly/overgrowth
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • Rabin-Pappas syndrome
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome
    Inheritance: AD Classification: STRONG Submitted by: ClinGen
  • Sotos syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • intellectual developmental disorder, autosomal dominant 70
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETD2NM_014159.7 linkc.6110-30_6110-26delAAAAA intron_variant Intron 13 of 20 ENST00000409792.4 NP_054878.5 Q9BYW2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETD2ENST00000409792.4 linkc.6110-30_6110-26delAAAAA intron_variant Intron 13 of 20 5 NM_014159.7 ENSP00000386759.3 Q9BYW2-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000164
AC:
2
AN:
1219822
Hom.:
0
AF XY:
0.00000165
AC XY:
1
AN XY:
604924
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
25788
American (AMR)
AF:
0.00
AC:
0
AN:
27124
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19922
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35366
South Asian (SAS)
AF:
0.00
AC:
0
AN:
65202
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45448
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4788
European-Non Finnish (NFE)
AF:
0.00000211
AC:
2
AN:
945862
Other (OTH)
AF:
0.00
AC:
0
AN:
50322
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.250
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.9
BranchPoint Hunter
1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs10589946; hg19: chr3-47103861; API