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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014159.7(SETD2):c.4918-44_4918-43del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 720,254 control chromosomes in the GnomAD database, including 1,790 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.15 ( 1437 hom., cov: 0)

Exomes 𝑓: 0.14 ( 353 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.996

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-47101597-AGT-A is Benign according to our data. Variant chr3-47101597-AGT-A is described in ClinVar as [Likely_benign]. Clinvar id is 436680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD2	NM_014159.7 linkuse as main transcript	c.4918-44_4918-43del		intron_variant		ENST00000409792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD2	ENST00000409792.4 linkuse as main transcript	c.4918-44_4918-43del		intron_variant		5	NM_014159.7	P3	Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

20853

AN:

141314

Hom.:

1439

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.0591

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.0954

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.186

AC:

22665

AN:

122034

Hom.:

128

AF XY:

0.192

AC XY:

12761

AN XY:

66322

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.185

GnomAD4 exome

AF:

0.142

AC:

82145

AN:

578844

Hom.:

353

AF XY:

0.144

AC XY:

44403

AN XY:

308346

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.0956

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.148

AC:

20865

AN:

141410

Hom.:

1437

Cov.:

AF XY:

0.146

AC XY:

10015

AN XY:

68518

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0884

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.0591

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.147

Gnomad4 OTH

AF:

0.143

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 29, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

4.0

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