dbSNP rs2015: SIRT2:c.*426A>C (chr19-38878729-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012237.4(SIRT2):c.*426A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 157,442 control chromosomes in the GnomAD database, including 17,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17144 hom., cov: 33)

Exomes 𝑓: 0.39 ( 435 hom. )

Consequence

SIRT2
NM_012237.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.27

Publications

42 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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new If you want to explore the variant's impact on the transcript NM_012237.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-38878729-T-G is Benign according to our data. Variant chr19-38878729-T-G is described in ClinVar as Benign. ClinVar VariationId is 1269273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 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.*426A>C	3_prime_UTR	Exon 16 of 16	NP_036369.2
SIRT2	NM_030593.3		c.*426A>C	3_prime_UTR	Exon 15 of 15	NP_085096.1	Q8IXJ6-2
SIRT2	NM_001193286.2		c.*628A>C	3_prime_UTR	Exon 13 of 13	NP_001180215.1	A0A0A0MRF5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SIRT2	ENST00000249396.12	TSL:1 MANE Select	c.*426A>C	3_prime_UTR	Exon 16 of 16	ENSP00000249396.7	Q8IXJ6-1
SIRT2	ENST00000392081.6	TSL:1	c.*426A>C	3_prime_UTR	Exon 15 of 15	ENSP00000375931.2	Q8IXJ6-2
SIRT2	ENST00000462654.5	TSL:1	n.2367A>C	non_coding_transcript_exon	Exon 13 of 13

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71074

AN:

151938

Hom.:

17116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.574

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.463

GnomAD4 exome

AF:

0.386

AC:

2078

AN:

5386

Hom.:

435

Cov.:

AF XY:

0.389

AC XY:

1106

AN XY:

2846

show subpopulations

African (AFR)

AF:

0.577

AC:

AN:

156

American (AMR)

AF:

0.536

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

AN:

162

East Asian (EAS)

AF:

0.432

AC:

AN:

162

South Asian (SAS)

AF:

0.424

AC:

217

AN:

512

European-Finnish (FIN)

AF:

0.330

AC:

AN:

182

Middle Eastern (MID)

AF:

0.278

AC:

AN:

European-Non Finnish (NFE)

AF:

0.366

AC:

1360

AN:

3720

Other (OTH)

AF:

0.413

AC:

161

AN:

390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.468

AC:

71157

AN:

152056

Hom.:

17144

Cov.:

AF XY:

0.468

AC XY:

34755

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.573

AC:

23805

AN:

41510

American (AMR)

AF:

0.488

AC:

7459

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1679

AN:

3470

East Asian (EAS)

AF:

0.512

AC:

2636

AN:

5146

South Asian (SAS)

AF:

0.490

AC:

2364

AN:

4822

European-Finnish (FIN)

AF:

0.381

AC:

4029

AN:

10578

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.408

AC:

27743

AN:

67940

Other (OTH)

AF:

0.470

AC:

993

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1959

3918

5877

7836

9795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.430

Hom.:

50723

Bravo

AF:

0.481

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.47

(source)

DANN

Benign

0.52

PhyloP100

-2.3

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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