dbSNP rs202127838: SIRT2:p.Glu379* (chr19-38879190-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012237.4(SIRT2):c.1135G>T(p.Glu379*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SIRT2
NM_012237.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.940

Publications

0 publications found

Variant links:

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]

SIRT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012237.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIRT2	NM_012237.4	MANE Select	c.1135G>T	p.Glu379*	stop_gained	Exon 16 of 16	NP_036369.2
SIRT2	NM_030593.3		c.1024G>T	p.Glu342*	stop_gained	Exon 15 of 15	NP_085096.1	Q8IXJ6-2
SIRT2	NM_001193286.2		c.*167G>T		3_prime_UTR	Exon 13 of 13	NP_001180215.1	A0A0A0MRF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.1135G>T	p.Glu379*	stop_gained	Exon 16 of 16	ENSP00000249396.7	Q8IXJ6-1
SIRT2	ENST00000392081.6	TSL:1	c.1024G>T	p.Glu342*	stop_gained	Exon 15 of 15	ENSP00000375931.2	Q8IXJ6-2
SIRT2	ENST00000462654.5	TSL:1	n.1906G>T		non_coding_transcript_exon	Exon 13 of 13

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1434780

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31384

American (AMR)

AF:

0.00

AC:

AN:

34032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24576

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104874

Other (OTH)

AF:

0.00

AC:

AN:

59162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Benign

0.16

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.26

PhyloP100

0.94

Vest4

0.70

ClinPred

0.85

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=112/88

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over