19-38879251-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.05

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]

ACMG classification

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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT2	NM_012237.4	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	c.1074G>A	p.Ala358=	synonymous_variant	16/16	1	NM_012237.4	P4

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152154 Hom.: 1 Cov.: 33

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.: 3 AF XY: 0.00119 AC XY: 154 AN XY: 129556

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.: 2 Cov.: 32 AF XY: 0.000520 AC XY: 376 AN XY: 722884

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: 99 AN: 152272 Hom.: 1 Cov.: 33 AF XY: 0.000819 AC XY: 61 AN XY: 74452

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.: 0

Bravo AF: 0.000287

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.20
Dann	Benign	0.74
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0085	N
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
Sift4G	Benign	0.60	T
Vest4		0.16
MVP		0.27
ClinPred		0.032	T
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

Other links and lift over

dbSNP: rs142522547; hg19: chr19-39369891; COSMIC: COSV50874455; COSMIC: COSV50874455;