rs11575003

chr19-38897202-T-C

Variant summary

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

The NM_012237.4(SIRT2):c.63+1177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,114 control chromosomes in the GnomAD database, including 8,107 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 0.23 (8107 hom., cov: 32)
• Consequence: SIRT2 NM_012237.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIRT2	NM_012237.4	c.63+1177A>G		intron_variant		ENST00000249396.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIRT2	ENST00000249396.12	c.63+1177A>G		intron_variant		1	NM_012237.4	P4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34584 AN: 151994 Hom.: 8087 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.228 AC: 34643 AN: 152114 Hom.: 8107 Cov.: 32 AF XY: 0.224 AC XY: 16690 AN XY: 74368

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0944

Gnomad4 NFE AF: 0.0685

Gnomad4 OTH AF: 0.200

Alfa AF: 0.170 Hom.: 748

Bravo AF: 0.244

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.0
Dann	Benign	0.56

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: rs11575003; hg19: chr19-39387842;