NM_014159.7:c.2632G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014159.7(SETD2):​c.2632G>C​(p.Gly878Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SETD2
NM_014159.7 missense

Scores

19

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.112
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.066013426).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETD2NM_014159.7 linkc.2632G>C p.Gly878Arg 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
SETD2ENST00000409792.4 linkc.2632G>C p.Gly878Arg missense_variant Exon 3 of 21 5 NM_014159.7 ENSP00000386759.3 Q9BYW2-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461616
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727092
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
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
0.10
BayesDel_addAF
Benign
-0.0081
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
14
DANN
Benign
0.96
DEOGEN2
Benign
0.078
T;T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.31
N;N
REVEL
Benign
0.18
Sift
Benign
0.073
T;T
Sift4G
Benign
0.15
T;.
Polyphen
0.0
B;.
Vest4
0.057
MutPred
0.23
Gain of glycosylation at S876 (P = 0.0474);.;
MVP
0.53
MPC
0.36
ClinPred
0.026
T
GERP RS
-0.66
Varity_R
0.042
gMVP
0.27

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.

Other links and lift over

dbSNP: rs587778671; hg19: chr3-47163494; API