rs2015

chr19-38878729-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012237.4(SIRT2):c.*426A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 157,442 control chromosomes in the GnomAD database, including 17,579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17144 hom., cov: 33)
  • Exomes 𝑓: 0.39 (435 hom.)
• Consequence: SIRT2 NM_012237.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.27

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-38878729-T-G is Benign according to our data. Variant chr19-38878729-T-G is described in ClinVar as [Benign]. Clinvar id is 1269273.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
SIRT2	NM_012237.4	c.*426A>C		3_prime_UTR_variant	16/16	ENST00000249396.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT2	ENST00000249396.12	c.*426A>C		3_prime_UTR_variant	16/16	1	NM_012237.4	P4

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

Gnomad4 AFR exome AF: 0.577

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.413

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

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.470

Alfa AF: 0.426 Hom.: 23427

Bravo AF: 0.481

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

GeneDx

Feb 18, 2020

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
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: rs2015; hg19: chr19-39369369;