rs2015

Variant names:

• chr19-38878729-T-G
• rs2015
• ENST00000462654.5:n.2367A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462654.5(SIRT2):​n.2367A>C variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17144 hom., cov: 33)
  • Exomes 𝑓: 0.39 (435 hom.)
• Consequence: SIRT2 ENST00000462654.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.27
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIRT2	NM_012237.4	c.*426A>C		3_prime_UTR_variant	Exon 16 of 16	ENST00000249396.12	NP_036369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIRT2	ENST00000249396.12	c.*426A>C		3_prime_UTR_variant	Exon 16 of 16	1	NM_012237.4	ENSP00000249396.7

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71074 AN: 151938 Hom.: 17116 Cov.: 33

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.: 0 AF XY: 0.389 AC XY: 1106 AN XY: 2846

African (AFR) AF: 0.577 AC: 90 AN: 156

American (AMR) AF: 0.536 AC: 45 AN: 84

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 70 AN: 162

East Asian (EAS) AF: 0.432 AC: 70 AN: 162

South Asian (SAS) AF: 0.424 AC: 217 AN: 512

European-Finnish (FIN) AF: 0.330 AC: 60 AN: 182

Middle Eastern (MID) AF: 0.278 AC: 5 AN: 18

European-Non Finnish (NFE) AF: 0.366 AC: 1360 AN: 3720

Other (OTH) AF: 0.413 AC: 161 AN: 390

GnomAD4 genome AF: 0.468 AC: 71157 AN: 152056 Hom.: 17144 Cov.: 33 AF XY: 0.468 AC XY: 34755 AN XY: 74320

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

Alfa AF: 0.430 Hom.: 50723

Bravo AF: 0.481

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31214610) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.47
DANN	Benign	0.52
PhyloP100		-2.3
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2015; hg19: chr19-39369369;