chr19-38879656-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012237.4(SIRT2):c.923A>T(p.Asp308Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000318 in 1,574,526 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
SIRT2
NM_012237.4 missense
NM_012237.4 missense
Scores
3
10
5
Clinical Significance
Conservation
PhyloP100: 7.09
Genes affected
SIRT2 (HGNC:10886): (sirtuin 2) This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Several transcript variants are resulted from alternative splicing of this gene. [provided by RefSeq, Jul 2010]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIRT2 | NM_012237.4 | c.923A>T | p.Asp308Val | missense_variant | 14/16 | ENST00000249396.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIRT2 | ENST00000249396.12 | c.923A>T | p.Asp308Val | missense_variant | 14/16 | 1 | NM_012237.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 151940Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 7.03e-7 AC: 1AN: 1422586Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 704218
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 151940Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74196
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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 | Mar 07, 2024 | The c.923A>T (p.D308V) alteration is located in exon 14 (coding exon 14) of the SIRT2 gene. This alteration results from a A to T substitution at nucleotide position 923, causing the aspartic acid (D) at amino acid position 308 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.
REVEL
Uncertain
Sift
Benign
T;T;.
Sift4G
Benign
T;.;T
Polyphen
B;B;.
Vest4
MutPred
Loss of disorder (P = 0.015);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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