Variant chr19-38879251-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_012237.4(SIRT2):c.1074G>A(p.Ala358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000559 in 1,604,580 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 2 hom. )

Consequence

SIRT2
NM_012237.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.05

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041135848).

BP6

Variant 19-38879251-C-T is Benign according to our data. Variant chr19-38879251-C-T is described in ClinVar as [Benign]. Clinvar id is 745830.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-7.05 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT2	NM_012237.4 linkuse as main transcript	c.1074G>A	p.Ala358=	synonymous_variant	16/16	ENST00000249396.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT2	ENST00000249396.12 linkuse as main transcript	c.1074G>A	p.Ala358=	synonymous_variant	16/16	1	NM_012237.4	P4	Q8IXJ6-1

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00122

AC:

290

AN:

238076

Hom.:

AF XY:

0.00119

AC XY:

154

AN XY:

129556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00462

Gnomad SAS exome

AF:

0.0000681

Gnomad FIN exome

AF:

0.00612

Gnomad NFE exome

AF:

0.000601

Gnomad OTH exome

AF:

0.00190

GnomAD4 exome

AF:

0.000549

AC:

798

AN:

1452308

Hom.:

Cov.:

AF XY:

0.000520

AC XY:

376

AN XY:

722884

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00499

Gnomad4 SAS exome

AF:

0.000141

Gnomad4 FIN exome

AF:

0.00574

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.000967

GnomAD4 genome

AF:

0.000650

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00522

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.000287

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00124

AC:

151

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

May 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.20

DANN

Benign

0.74

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0085

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

Sift4G

Benign

0.60

Vest4

0.16

MVP

0.27

ClinPred

0.032

GERP RS

-9.2

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

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