rs11717033

chr3-47126729-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014159.7(SETD2):c.72-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 927,100 control chromosomes in the GnomAD database, including 935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (95 hom., cov: 32)
  • Exomes 𝑓: 0.042 (840 hom.)
• Consequence: SETD2 NM_014159.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.247

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-47126729-T-C is Benign according to our data. Variant chr3-47126729-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1187337.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETD2	NM_014159.7	c.72-66A>G		intron_variant		ENST00000409792.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETD2	ENST00000409792.4	c.72-66A>G		intron_variant		5	NM_014159.7	P3
SETD2	ENST00000412450.1	c.-61-66A>G		intron_variant		2
SETD2	ENST00000638947.2	c.-45-2181A>G		intron_variant		5		A2
SETD2	ENST00000691544.1	c.72-28648A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4604 AN: 152190 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.00929

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0812

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.0417 AC: 32304 AN: 774792 Hom.: 840 AF XY: 0.0424 AC XY: 17160 AN XY: 404278

Gnomad4 AFR exome AF: 0.00750

Gnomad4 AMR exome AF: 0.0166

Gnomad4 ASJ exome AF: 0.0762

Gnomad4 EAS exome AF: 0.0000305

Gnomad4 SAS exome AF: 0.0482

Gnomad4 FIN exome AF: 0.0170

Gnomad4 NFE exome AF: 0.0465

Gnomad4 OTH exome AF: 0.0394

GnomAD4 genome AF: 0.0302 AC: 4603 AN: 152308 Hom.: 95 Cov.: 32 AF XY: 0.0285 AC XY: 2124 AN XY: 74492

Gnomad4 AFR AF: 0.00924

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0812

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0518

Gnomad4 FIN AF: 0.0133

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0450 Hom.: 196

Bravo AF: 0.0292

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.63
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs11717033; hg19: chr3-47168219;