Variant 3-47062371-GTTTT-GTT 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.6110-27_6110-26delAA 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 0.65 ( 30949 hom., cov: 0)

Exomes 𝑓: 0.50 ( 91665 hom. )

Failed GnomAD Quality Control

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.247

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 -16 ACMG points.

BP6

Variant 3-47062371-GTT-G is Benign according to our data. Variant chr3-47062371-GTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 436678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 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.6110-27_6110-26delAA		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.6110-27_6110-26delAA		intron_variant		5	NM_014159.7	ENSP00000386759.3		Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

95392

AN:

146624

Hom.:

30910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.744

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.517

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.625

GnomAD3 exomes

AF:

0.593

AC:

87781

AN:

147998

Hom.:

20237

AF XY:

0.584

AC XY:

46833

AN XY:

80146

show subpopulations

Gnomad AFR exome

AF:

0.674

Gnomad AMR exome

AF:

0.701

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.635

Gnomad SAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.596

Gnomad NFE exome

AF:

0.563

Gnomad OTH exome

AF:

0.570

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.497

AC:

603584

AN:

1214838

Hom.:

91665

AF XY:

0.496

AC XY:

298751

AN XY:

602492

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.647

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.602

Gnomad4 SAS exome

AF:

0.494

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.499

GnomAD4 genome

AF:

0.651

AC:

95462

AN:

146674

Hom.:

30949

Cov.:

AF XY:

0.649

AC XY:

46319

AN XY:

71330

show subpopulations

Gnomad4 AFR

AF:

0.745

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.591

Gnomad4 EAS

AF:

0.689

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.634

Gnomad4 NFE

AF:

0.600

Gnomad4 OTH

AF:

0.626

Bravo

AF:

0.654

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

- -

Luscan-Lumish syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Mar 15, 2022

- -

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

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