3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGT

Position:

• chr3-47101597-AGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014159.7(SETD2):​c.4918-44_4918-43dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.28 (5080 hom., cov: 0)
  • Exomes 𝑓: 0.12 (236 hom.)
• Consequence: SETD2 NM_014159.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.533

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-47101597-A-AGT is Benign according to our data. Variant chr3-47101597-A-AGT is described in ClinVar as [Benign]. Clinvar id is 1230666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SETD2	NM_014159.7	c.4918-44_4918-43dupAC		intron_variant		ENST00000409792.4	NP_054878.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SETD2	ENST00000409792.4	c.4918-44_4918-43dupAC		intron_variant		5	NM_014159.7	ENSP00000386759.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 39243 AN: 141348 Hom.: 5074 Cov.: 0

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.145 AC: 17743 AN: 122034 Hom.: 206 AF XY: 0.143 AC XY: 9496 AN XY: 66322

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.118 AC: 69534 AN: 589510 Hom.: 236 Cov.: 0 AF XY: 0.119 AC XY: 37384 AN XY: 314140

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0978

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0755

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.278 AC: 39288 AN: 141446 Hom.: 5080 Cov.: 0 AF XY: 0.273 AC XY: 18687 AN XY: 68550

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.278

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61571386; hg19: chr3-47143087;