Variant 3-47017841-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014159.7(SETD2):c.7432-102A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00809 in 800,810 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 43 hom. )

Consequence

SETD2
NM_014159.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.196

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-47017841-T-A is Benign according to our data. Variant chr3-47017841-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1192016.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00667 (1016/152272) while in subpopulation NFE AF= 0.0119 (810/68028). AF 95% confidence interval is 0.0112. There are 10 homozygotes in gnomad4. There are 451 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1016 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD2	NM_014159.7 linkuse as main transcript	c.7432-102A>T		intron_variant		ENST00000409792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD2	ENST00000409792.4 linkuse as main transcript	c.7432-102A>T		intron_variant		5	NM_014159.7	P3	Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.00668

AC:

1016

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00383

GnomAD4 exome

AF:

0.00843

AC:

5465

AN:

648538

Hom.:

AF XY:

0.00811

AC XY:

2806

AN XY:

345836

show subpopulations

Gnomad4 AFR exome

AF:

0.00241

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.000753

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00106

Gnomad4 FIN exome

AF:

0.000785

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.00878

GnomAD4 genome

AF:

0.00667

AC:

1016

AN:

152272

Hom.:

Cov.:

AF XY:

0.00606

AC XY:

451

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00287

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00873

Hom.:

Bravo

AF:

0.00666

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Oct 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.53

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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