rs45592833

Positions:

• chr19-38878995-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012237.4(SIRT2):​c.*160C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 675,324 control chromosomes in the GnomAD database, including 451 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 0.039 (333 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (118 hom.)
• Consequence: SIRT2 NM_012237.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIRT2	NM_012237.4	c.*160C>A		3_prime_UTR_variant	16/16	ENST00000249396.12	NP_036369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIRT2	ENST00000249396.12	c.*160C>A		3_prime_UTR_variant	16/16	1	NM_012237.4	ENSP00000249396	P4

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5962 AN: 151936 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.00892

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.00784 AC: 4100 AN: 523270 Hom.: 118 Cov.: 7 AF XY: 0.00763 AC XY: 2068 AN XY: 271078

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.00573

Gnomad4 EAS exome AF: 0.00630

Gnomad4 SAS exome AF: 0.00809

Gnomad4 FIN exome AF: 0.00245

Gnomad4 NFE exome AF: 0.00340

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0394 AC: 5987 AN: 152054 Hom.: 333 Cov.: 32 AF XY: 0.0371 AC XY: 2760 AN XY: 74356

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0180

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.0101

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0244 Hom.: 26

Bravo AF: 0.0448

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs45592833; hg19: chr19-39369635;