3-47057329-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014159.7(SETD2):​c.6455A>C​(p.Tyr2152Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SETD2
NM_014159.7 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETD2NM_014159.7 linkc.6455A>C p.Tyr2152Ser missense_variant Exon 15 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.6455A>C p.Tyr2152Ser missense_variant Exon 15 of 21 5 NM_014159.7 ENSP00000386759.3 Q9BYW2-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
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:
0.0000374
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.47
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.15
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.030
D
Polyphen
0.98
D
Vest4
0.53
MutPred
0.24
Gain of glycosylation at Y2152 (P = 0.0011);
MVP
0.33
MPC
0.91
ClinPred
0.86
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.31
gMVP
0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-47098819; API