rs2241703

chr19-38878874-G-Achr19-38878874-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.*281C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 369,814 control chromosomes in the GnomAD database, including 384 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 0.0055 (40 hom., cov: 33)
  • Exomes 𝑓: 0.016 (344 hom.)
• Consequence: SIRT2 NM_012237.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT2	NM_012237.4	c.*281C>T		3_prime_UTR_variant	16/16	ENST00000249396.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT2	ENST00000249396.12	c.*281C>T		3_prime_UTR_variant	16/16	1	NM_012237.4	P4

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 841 AN: 152216 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.0159 AC: 3448 AN: 217478 Hom.: 344 Cov.: 0 AF XY: 0.0148 AC XY: 1635 AN XY: 110350

Gnomad4 AFR exome AF: 0.000338

Gnomad4 AMR exome AF: 0.00106

Gnomad4 ASJ exome AF: 0.00457

Gnomad4 EAS exome AF: 0.192

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.00572

Gnomad4 NFE exome AF: 0.000364

Gnomad4 OTH exome AF: 0.00734

GnomAD4 genome AF: 0.00551 AC: 840 AN: 152336 Hom.: 40 Cov.: 33 AF XY: 0.00593 AC XY: 442 AN XY: 74486

Gnomad4 AFR AF: 0.000697

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00659

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.000411 Hom.: 2

Bravo AF: 0.00558

Asia WGS AF: 0.0390 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.8
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2241703; hg19: chr19-39369514;