Variant 3-47062371-GTTTT-GTTT 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.6110-26delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 0)

Exomes 𝑓: 0.050 ( 5 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.577

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 3-47062371-GT-G is Benign according to our data. Variant chr3-47062371-GT-G is described in ClinVar as [Benign]. Clinvar id is 1178301.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0703 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.6110-26delA		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.6110-26delA		intron_variant		5	NM_014159.7	ENSP00000386759.3		Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

514

AN:

146620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00884

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00181

Gnomad ASJ

AF:

0.000588

Gnomad EAS

AF:

0.00316

Gnomad SAS

AF:

0.00238

Gnomad FIN

AF:

0.00210

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00494

GnomAD3 exomes

AF:

0.0373

AC:

5517

AN:

147998

Hom.:

AF XY:

0.0387

AC XY:

3105

AN XY:

80146

show subpopulations

Gnomad AFR exome

AF:

0.0384

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0565

Gnomad EAS exome

AF:

0.0359

Gnomad SAS exome

AF:

0.0558

Gnomad FIN exome

AF:

0.0242

Gnomad NFE exome

AF:

0.0347

Gnomad OTH exome

AF:

0.0486

GnomAD4 exome

AF:

0.0503

AC:

55293

AN:

1099224

Hom.:

Cov.:

AF XY:

0.0502

AC XY:

27349

AN XY:

544416

show subpopulations

Gnomad4 AFR exome

AF:

0.0733

Gnomad4 AMR exome

AF:

0.0348

Gnomad4 ASJ exome

AF:

0.0467

Gnomad4 EAS exome

AF:

0.0338

Gnomad4 SAS exome

AF:

0.0570

Gnomad4 FIN exome

AF:

0.0371

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.0505

GnomAD4 genome

AF:

0.00352

AC:

516

AN:

146672

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

215

AN XY:

71316

show subpopulations

Gnomad4 AFR

AF:

0.00885

Gnomad4 AMR

AF:

0.00181

Gnomad4 ASJ

AF:

0.000588

Gnomad4 EAS

AF:

0.00317

Gnomad4 SAS

AF:

0.00239

Gnomad4 FIN

AF:

0.00210

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00539

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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