dbSNP rs2082435: SIRT2:c.632-113G>C (chr19-38881604-C-G) – 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.632-113G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 795,514 control chromosomes in the GnomAD database, including 63,689 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 0.38 ( 11482 hom., cov: 30)

Exomes 𝑓: 0.40 ( 52207 hom. )

Consequence

SIRT2
NM_012237.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.387

Publications

8 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT2	NM_012237.4 link	c.632-113G>C		intron_variant	Intron 9 of 15	ENST00000249396.12	NP_036369.2	Q8IXJ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT2	ENST00000249396.12 link	c.632-113G>C		intron_variant	Intron 9 of 15	1	NM_012237.4	ENSP00000249396.7		Q8IXJ6-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58360

AN:

151796

Hom.:

11467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.408

GnomAD4 exome

AF:

0.396

AC:

254932

AN:

643600

Hom.:

52207

AF XY:

0.396

AC XY:

134981

AN XY:

340690

show subpopulations

African (AFR)

AF:

0.320

AC:

5551

AN:

17324

American (AMR)

AF:

0.574

AC:

19466

AN:

33914

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

7751

AN:

18810

East Asian (EAS)

AF:

0.282

AC:

9235

AN:

32722

South Asian (SAS)

AF:

0.394

AC:

24273

AN:

61590

European-Finnish (FIN)

AF:

0.405

AC:

19152

AN:

47258

Middle Eastern (MID)

AF:

0.469

AC:

1957

AN:

4170

European-Non Finnish (NFE)

AF:

0.391

AC:

154423

AN:

394660

Other (OTH)

AF:

0.396

AC:

13124

AN:

33152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7714

15429

23143

30858

38572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1920

3840

5760

7680

9600

<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:

0.385

AC:

58412

AN:

151914

Hom.:

11482

Cov.:

AF XY:

0.386

AC XY:

28681

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.320

AC:

13269

AN:

41438

American (AMR)

AF:

0.496

AC:

7559

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1384

AN:

3468

East Asian (EAS)

AF:

0.335

AC:

1728

AN:

5158

South Asian (SAS)

AF:

0.386

AC:

1855

AN:

4804

European-Finnish (FIN)

AF:

0.393

AC:

4148

AN:

10548

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27132

AN:

67928

Other (OTH)

AF:

0.406

AC:

859

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1791

3582

5372

7163

8954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.383

Hom.:

1436

Bravo

AF:

0.390

Asia WGS

AF:

0.402

AC:

1397

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.7

(source)

DANN

Benign

0.43

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over