Variant 19-38889130-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012237.4(SIRT2):c.458G>A(p.Arg153His) variant causes a missense change. The variant allele was found at a frequency of 0.00912 in 1,613,056 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 92 hom. )

Consequence

SIRT2
NM_012237.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.70

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009638488).

BP6

Variant 19-38889130-C-T is Benign according to our data. Variant chr19-38889130-C-T is described in ClinVar as [Benign]. Clinvar id is 784716.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT2	NM_012237.4 linkuse as main transcript	c.458G>A	p.Arg153His	missense_variant	8/16	ENST00000249396.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT2	ENST00000249396.12 linkuse as main transcript	c.458G>A	p.Arg153His	missense_variant	8/16	1	NM_012237.4	P4	Q8IXJ6-1

Frequencies

GnomAD3 genomes

AF:

0.00764

AC:

1162

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00735

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00863

AC:

2161

AN:

250314

Hom.:

AF XY:

0.00862

AC XY:

1167

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00693

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00928

AC:

13552

AN:

1460748

Hom.:

Cov.:

AF XY:

0.00912

AC XY:

6627

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.00722

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.00871

GnomAD4 genome

AF:

0.00763

AC:

1162

AN:

152308

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00735

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00727

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.00966

AC:

1173

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.84

MetaRNN

Benign

0.0096

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

REVEL

Benign

0.23

Polyphen

0.98, 0.99

.;D;D;.;.;.;.

Vest4

0.57

MVP

0.45

MPC

0.91

ClinPred

0.035

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over