Variant 3-47062371-GTTTT-GT details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014159.7(SETD2):c.6110-28_6110-26delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 1,344,060 control chromosomes in the GnomAD database, including 6 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 0.0028 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0077 ( 4 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00276 (405/146738) while in subpopulation AFR AF= 0.00606 (244/40238). AF 95% confidence interval is 0.00544. There are 2 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 405 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD2	NM_014159.7 linkuse as main transcript	c.6110-28_6110-26delAAA		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.6110-28_6110-26delAAA		intron_variant		5	NM_014159.7	ENSP00000386759.3		Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

407

AN:

146686

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000806

Gnomad ASJ

AF:

0.00323

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00216

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.000987

GnomAD3 exomes

AF:

0.00991

AC:

1467

AN:

147998

Hom.:

AF XY:

0.0100

AC XY:

805

AN XY:

80146

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.00776

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.00578

Gnomad SAS exome

AF:

0.0105

Gnomad FIN exome

AF:

0.00738

Gnomad NFE exome

AF:

0.00982

Gnomad OTH exome

AF:

0.00911

GnomAD4 exome

AF:

0.00770

AC:

9215

AN:

1197322

Hom.:

AF XY:

0.00751

AC XY:

4460

AN XY:

593878

show subpopulations

Gnomad4 AFR exome

AF:

0.0166

Gnomad4 AMR exome

AF:

0.00522

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.00330

Gnomad4 SAS exome

AF:

0.00888

Gnomad4 FIN exome

AF:

0.00736

Gnomad4 NFE exome

AF:

0.00755

Gnomad4 OTH exome

AF:

0.00800

GnomAD4 genome

AF:

0.00276

AC:

405

AN:

146738

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

181

AN XY:

71368

show subpopulations

Gnomad4 AFR

AF:

0.00606

Gnomad4 AMR

AF:

0.000805

Gnomad4 ASJ

AF:

0.00323

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00195

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.000979

Alfa

AF:

0.00178

Hom.:

890

ClinVar

Not reported in ClinVar

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over