3-47121932-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014159.7(SETD2):c.2704G>C(p.Glu902Gln) variant causes a missense change. The variant allele was found at a frequency of 0.012 in 1,613,906 control chromosomes in the GnomAD database, including 1,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 1026 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 956 hom. )

Consequence

SETD2
NM_014159.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 4.82

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015663505).

BP6

Variant 3-47121932-C-G is Benign according to our data. Variant chr3-47121932-C-G is described in ClinVar as [Benign]. Clinvar id is 135230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-47121932-C-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD2	NM_014159.7 link	c.2704G>C	p.Glu902Gln	missense_variant	Exon 3 of 21	ENST00000409792.4	NP_054878.5	Q9BYW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD2	ENST00000409792.4 link	c.2704G>C	p.Glu902Gln	missense_variant	Exon 3 of 21	5	NM_014159.7	ENSP00000386759.3		Q9BYW2-1

Frequencies

GnomAD3 genomes

AF:

0.0632

AC:

9617

AN:

152116

Hom.:

1020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0167

AC:

4186

AN:

250786

Hom.:

452

AF XY:

0.0124

AC XY:

1686

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000565

Gnomad OTH exome

AF:

0.00868

GnomAD4 exome

AF:

0.00662

AC:

9674

AN:

1461672

Hom.:

956

Cov.:

AF XY:

0.00571

AC XY:

4149

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.0138

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000349

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.0633

AC:

9637

AN:

152234

Hom.:

1026

Cov.:

AF XY:

0.0603

AC XY:

4489

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.0307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.00480

Hom.:

Bravo

AF:

0.0738

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.209

AC:

923

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0203

AC:

2466

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.000981

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Luscan-Lumish syndrome

Benign:2

Mar 15, 2022

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Aug 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1Other:1

Jun 26, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.21

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.040

D;.

Polyphen

0.98

D;.

Vest4

0.046

MPC

0.44

ClinPred

0.033

GERP RS

5.1

Varity_R

0.24

gMVP

0.39

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