rs4802998

chr19-38897076-G-Achr19-38897076-G-Cchr19-38897076-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.63+1303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,152 control chromosomes in the GnomAD database, including 39,416 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 0.71 (39416 hom., cov: 32)
• Consequence: SIRT2 NM_012237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT2	NM_012237.4	c.63+1303C>T		intron_variant		ENST00000249396.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT2	ENST00000249396.12	c.63+1303C>T		intron_variant		1	NM_012237.4	P4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108106 AN: 152034 Hom.: 39359 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.967

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.711 AC: 108219 AN: 152152 Hom.: 39416 Cov.: 32 AF XY: 0.719 AC XY: 53526 AN XY: 74394

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.967

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.607

Gnomad4 OTH AF: 0.700

Alfa AF: 0.649 Hom.: 17067

Bravo AF: 0.723

Asia WGS AF: 0.859 AC: 2985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	5.6
Dann	Benign	0.74

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: rs4802998; hg19: chr19-39387716;