GeneBe

rs61571386

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_014159.7(SETD2):​c.4918-66_4918-43delACACACACACACACACACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 734,106 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.0000071 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000061 ( 1 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26
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]

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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 sas. gnomad4_exome allele frequency = 0.0000608 (36/592436) while in subpopulation SAS AF= 0.000664 (34/51190). AF 95% confidence interval is 0.000488. There are 1 homozygotes in gnomad4_exome. There are 32 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 36 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SETD2NM_014159.7 linkuse as main transcriptc.4918-66_4918-43delACACACACACACACACACACACAC intron_variant ENST00000409792.4 NP_054878.5 Q9BYW2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SETD2ENST00000409792.4 linkuse as main transcriptc.4918-66_4918-43delACACACACACACACACACACACAC intron_variant 5 NM_014159.7 ENSP00000386759.3 Q9BYW2-1

Frequencies

GnomAD3 genomes
AF:
0.00000706
AC:
1
AN:
141572
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000229
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000608
AC:
36
AN:
592436
Hom.:
1
AF XY:
0.000101
AC XY:
32
AN XY:
315700
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000664
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000269
Gnomad4 OTH exome
AF:
0.0000340
GnomAD4 genome
AF:
0.00000706
AC:
1
AN:
141670
Hom.:
0
Cov.:
0
AF XY:
0.0000146
AC XY:
1
AN XY:
68672
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000230
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BranchPoint Hunter
4.0

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61571386; hg19: chr3-47143087; API