Genetic Variant SIRT2:c.64-1025A>G (chr19-38894892-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012237.4(SIRT2):c.64-1025A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 455,854 control chromosomes in the GnomAD database, including 97,140 homozygotes. 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: 𝑓 0.67 ( 35380 hom., cov: 29)

Exomes 𝑓: 0.63 ( 61760 hom. )

Consequence

SIRT2
NM_012237.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.620

Publications

49 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:

ENSG00000305081 (HGNC:):

ENSG00000305081 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
SIRT2	NM_012237.4	MANE Select	c.64-1025A>G	intron	N/A	NP_036369.2
SIRT2	NM_030593.3		c.-48-1025A>G	intron	N/A	NP_085096.1	Q8IXJ6-2
SIRT2	NM_001193286.2		c.-48-1025A>G	intron	N/A	NP_001180215.1	A0A0A0MRF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.64-1025A>G	intron	N/A	ENSP00000249396.7	Q8IXJ6-1
SIRT2	ENST00000392081.6	TSL:1	c.-48-1025A>G	intron	N/A	ENSP00000375931.2	Q8IXJ6-2
SIRT2	ENST00000872149.1		c.64-1025A>G	intron	N/A	ENSP00000542208.1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101517

AN:

151724

Hom.:

35329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.557

Gnomad AMR

AF:

0.731

Gnomad ASJ

AF:

0.685

Gnomad EAS

AF:

0.967

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.663

GnomAD2 exomes

AF:

0.675

AC:

86843

AN:

128598

AF XY:

0.669

show subpopulations

Gnomad AFR exome

AF:

0.835

Gnomad AMR exome

AF:

0.753

Gnomad ASJ exome

AF:

0.692

Gnomad EAS exome

AF:

0.970

Gnomad FIN exome

AF:

0.580

Gnomad NFE exome

AF:

0.548

Gnomad OTH exome

AF:

0.642

GnomAD4 exome

AF:

0.626

AC:

190408

AN:

304012

Hom.:

61760

Cov.:

AF XY:

0.631

AC XY:

109223

AN XY:

173104

show subpopulations

African (AFR)

AF:

0.823

AC:

7104

AN:

8628

American (AMR)

AF:

0.754

AC:

20571

AN:

27280

Ashkenazi Jewish (ASJ)

AF:

0.692

AC:

7469

AN:

10790

East Asian (EAS)

AF:

0.972

AC:

8948

AN:

9210

South Asian (SAS)

AF:

0.700

AC:

41801

AN:

59742

European-Finnish (FIN)

AF:

0.581

AC:

7197

AN:

12390

Middle Eastern (MID)

AF:

0.672

AC:

1870

AN:

2782

European-Non Finnish (NFE)

AF:

0.544

AC:

86449

AN:

158942

Other (OTH)

AF:

0.632

AC:

8999

AN:

14248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

4674

9347

14021

18694

23368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

598

1196

1794

2392

2990

<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

AF:

0.669

AC:

101624

AN:

151842

Hom.:

35380

Cov.:

AF XY:

0.677

AC XY:

50241

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.828

AC:

34263

AN:

41394

American (AMR)

AF:

0.732

AC:

11161

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

2376

AN:

3470

East Asian (EAS)

AF:

0.967

AC:

4971

AN:

5142

South Asian (SAS)

AF:

0.717

AC:

3443

AN:

4800

European-Finnish (FIN)

AF:

0.605

AC:

6392

AN:

10562

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.544

AC:

36912

AN:

67908

Other (OTH)

AF:

0.666

AC:

1405

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1579

3158

4736

6315

7894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.591

Hom.:

46269

Bravo

AF:

0.687

Asia WGS

AF:

0.845

AC:

2935

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.7

(source)

DANN

Benign

0.84

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over