Variant 3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGTGT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_014159.7(SETD2):c.4918-46_4918-43dupACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.031 ( 61 hom., cov: 0)

Exomes 𝑓: 0.016 ( 15 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.533

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 links:

SETD2 (HGNC:):

SETD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-47101597-A-AGTGT is Benign according to our data. Variant chr3-47101597-A-AGTGT is described in ClinVar as [Likely_benign]. Clinvar id is 1220335.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD2	NM_014159.7 linkuse as main transcript	c.4918-46_4918-43dupACAC		intron_variant		ENST00000409792.4	NP_054878.5	Q9BYW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD2	ENST00000409792.4 linkuse as main transcript	c.4918-46_4918-43dupACAC		intron_variant		5	NM_014159.7	ENSP00000386759.3		Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4334

AN:

141520

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.0103

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.0682

Gnomad SAS

AF:

0.0305

Gnomad FIN

AF:

0.0435

Gnomad MID

AF:

0.0461

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0184

AC:

2248

AN:

122034

Hom.:

AF XY:

0.0180

AC XY:

1197

AN XY:

66322

show subpopulations

Gnomad AFR exome

AF:

0.0189

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.00826

Gnomad EAS exome

AF:

0.0380

Gnomad SAS exome

AF:

0.0139

Gnomad FIN exome

AF:

0.0278

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0174

GnomAD4 exome

AF:

0.0157

AC:

9280

AN:

591338

Hom.:

Cov.:

AF XY:

0.0157

AC XY:

4951

AN XY:

315120

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.0492

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0279

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.0307

AC:

4342

AN:

141618

Hom.:

Cov.:

AF XY:

0.0317

AC XY:

2176

AN XY:

68644

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.0298

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.0682

Gnomad4 SAS

AF:

0.0308

Gnomad4 FIN

AF:

0.0435

Gnomad4 NFE

AF:

0.0271

Gnomad4 OTH

AF:

0.0323

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

Aug 10, 2019

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over