chr13-49490879-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001160308.3(SETDB2):c.1975A>G(p.Asn659Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SETDB2
NM_001160308.3 missense
NM_001160308.3 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 2.18
Genes affected
SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38656166).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETDB2 | NM_001160308.3 | c.1975A>G | p.Asn659Asp | missense_variant | 13/14 | ENST00000611815.2 | |
SETDB2-PHF11 | NR_135324.2 | n.2631A>G | non_coding_transcript_exon_variant | 12/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETDB2 | ENST00000611815.2 | c.1975A>G | p.Asn659Asp | missense_variant | 13/14 | 5 | NM_001160308.3 | P1 | |
SETDB2 | ENST00000354234.8 | c.2011A>G | p.Asn671Asp | missense_variant | 14/15 | 1 | |||
SETDB2 | ENST00000317257.12 | c.1975A>G | p.Asn659Asp | missense_variant | 12/13 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250754Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135572
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461150Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2AN XY: 726892
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GnomAD4 genome ? AF: 0.0000459 AC: 7AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74496
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2021 | The c.2011A>G (p.N671D) alteration is located in exon 14 (coding exon 13) of the SETDB2 gene. This alteration results from a A to G substitution at nucleotide position 2011, causing the asparagine (N) at amino acid position 671 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
REVEL
Uncertain
Sift4G
Benign
T;T;T
Polyphen
D;D;.
Vest4
MVP
MPC
0.85
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at